{"title":"Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model.","authors":"Ayano Tobe-Nishimoto, Yoshihiro Morita, Junya Nishimura, Yukiko Kitahira, Shun Takayama, Satoko Kishimoto, Yuka Matsumiya-Matsumoto, Kazuhide Matsunaga, Tomoaki Imai, Narikazu Uzawa","doi":"10.1007/s10585-024-10306-1","DOIUrl":"10.1007/s10585-024-10306-1","url":null,"abstract":"<p><p>The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"891-908"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors associated with the distribution of brain metastases in lung cancer: a retrospective study.","authors":"Yixin Hu, Weiwei Lei, Enhui Xin, Tan Cheng, Jiang Liu, Yu Tang, Yong Lai, Hong Yu, Yong Tan, Jing Yang, Junhao Huang, Daihong Liu, Jiuquan Zhang","doi":"10.1007/s10585-024-10315-0","DOIUrl":"10.1007/s10585-024-10315-0","url":null,"abstract":"<p><p>The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"959-969"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed H Elbahoty, Bhavyasree Papineni, Rajeev S Samant
{"title":"Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics.","authors":"Mohamed H Elbahoty, Bhavyasree Papineni, Rajeev S Samant","doi":"10.1007/s10585-024-10305-2","DOIUrl":"10.1007/s10585-024-10305-2","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, the prevalence of MM has been steadily increasing at an alarming rate. In the United States, more than 30,000 cases will be diagnosed in 2024 and it accounts for about 2% of cancer diagnoses and more than 2% of cancer deaths, more than double the worldwide figure. Both symptomatic and active MM are distinguished by uncontrolled plasma cell growth, which results in severe renal impairment, anemia, hypercalcemia, and bone loss. Multiple drugs have been approved by the FDA and are now widely used in clinical practice for MM. Although triplet and quadruplet induction regimens, autologous stem cell transplantation (ASCT), and maintenance treatment are used, MM continues to be an incurable illness characterized by relapses that may occur at various phases of its progression. MM patients with frailty, extramedullary disease, plasma cell leukemia, central nervous system recurrence, functional high risk, and the elderly are among those with the greatest current unmet needs. The high cost of care is an additional challenge. MM cells are highly protein secretary cells and thus are dependent on the activation of certain translation pathways. MM also has a high chance of altering ribosomal protein-encoding genes like MYC mutation. In this article we discuss the importance of ribosome biogenesis in promoting MM and RNA polymerase I inhibition as an upcoming treatment with potential promise for MM patients.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"829-842"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingming Jin, Menghan Wang, Yulin Luo, Taile Yuan, Xue Li, Gang Huang, Qingqing Huang, Hong Sun
{"title":"Downregulation of hsa_circ_0006620 inhibits the malignant progression of prostate cancer by regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.","authors":"Mingming Jin, Menghan Wang, Yulin Luo, Taile Yuan, Xue Li, Gang Huang, Qingqing Huang, Hong Sun","doi":"10.1007/s10585-024-10314-1","DOIUrl":"10.1007/s10585-024-10314-1","url":null,"abstract":"<p><p>Circular RNAs (circRNA) are a class of covalently-closed, single-stranded RNAs that have been implicated in cancer progression due to their regulation of metabolism. However, the roles of circRNA in prostate cancer remain largely unknown. In this study, fluorescence in situ hybridization and RT-qPCR were used to investigate hsa_circ_0006620 expressions in both prostate cancer cells and tissues, after high-throughput sequencing. The luciferase reporter assay was used to identify hsa_circ_0006620 downstream targets. Transwell migration assays, 5-ethynyl-20-deoxyuridine assays, and Cell Counting Kit-8assays were used to investigate both proliferation and migration. In vivo tumorigenesis and metastasis assays were performed to investigate the role of hsa_circ_0006620 in prostate cancer. The results showed that hsa_circ_0006620 expression increased in prostate cancer cells and tissues. Hsa_circ_0006620 downregulation inhibited prostate cancer cell proliferation as well as in vivo and in vitro migrations. The luciferase results validated that miR-502-3p and hexokinase 2 (HK2) were hsa_circ_0006620 downstream targets. HK2 overexpression or miR-502-3p inhibition reversed prostate cancer cell migration after hsa_circ_0006620 silencing. The study also found that overexpression of HK2 or inhibition of prostate cancer reversed aerobic glycolysis after hsa_circ_0006620 silencing. In summary, the results showed thathsa_circ_0006620 downregulation inhibited prostate cancerby regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"947-958"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aaron G Baugh, Edgar Gonzalez, Valerie H Narumi, Jesse Kreger, Yingtong Liu, Christine Rafie, Sofi Castanon, Julie Jang, Luciane T Kagohara, Dimitra P Anastasiadou, James Leatherman, Todd Armstrong, Isaac Chan, George S Karagiannis, Elizabeth M Jaffee, Adam MacLean, Evanthia T Roussos Torres
{"title":"A new Neu-a syngeneic model of spontaneously metastatic HER2-positive breast cancer.","authors":"Aaron G Baugh, Edgar Gonzalez, Valerie H Narumi, Jesse Kreger, Yingtong Liu, Christine Rafie, Sofi Castanon, Julie Jang, Luciane T Kagohara, Dimitra P Anastasiadou, James Leatherman, Todd Armstrong, Isaac Chan, George S Karagiannis, Elizabeth M Jaffee, Adam MacLean, Evanthia T Roussos Torres","doi":"10.1007/s10585-024-10289-z","DOIUrl":"10.1007/s10585-024-10289-z","url":null,"abstract":"<p><p>Metastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN-the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"733-746"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa-Marie Mehner, Leonel Munoz-Sagredo, Steffen Joachim Sonnentag, Sven Máté Treffert, Véronique Orian-Rousseau
{"title":"Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.","authors":"Lisa-Marie Mehner, Leonel Munoz-Sagredo, Steffen Joachim Sonnentag, Sven Máté Treffert, Véronique Orian-Rousseau","doi":"10.1007/s10585-024-10292-4","DOIUrl":"10.1007/s10585-024-10292-4","url":null,"abstract":"<p><p>Although progress has been made in the treatment of cancer, particularly for the four major types of cancers affecting the lungs, colon, breast and prostate, resistance to cancer treatment often emerges upon inhibition of major signaling pathways, which leads to the activation of additional pathways as a last-resort survival mechanism by the cancer cells. This signaling plasticity provides cancer cells with a level of operational freedom, reducing treatment efficacy. Plasticity is a characteristic of cancer cells that are not only able to switch signaling pathways but also from one cellular state (differentiated cells to stem cells or vice versa) to another. It seems implausible that the inhibition of one or a few signaling pathways of heterogeneous and plastic tumors can sustain a durable effect. We propose that inhibiting molecules with pleiotropic functions such as cell surface co-receptors can be a key to preventing therapy escape instead of targeting bona fide receptors. Therefore, we ask the question whether co-receptors often considered as \"accessory molecules\" are an overlooked key to control cancer cell behavior.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"599-611"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Cuccia, Ciro Franzese, Serena Badellino, Paolo Borghetti, Manuela Federico, Giulia Marvaso, Giampaolo Montesi, Antonio Pontoriero, Giuseppe Ferrera, Filippo Alongi, Marta Scorsetti
{"title":"Stereotactic body radiotherapy for spinal oligometastases: a survey on patterns of practice on behalf of the Italian Association of Clinical Oncology and Radiotherapy (AIRO).","authors":"Francesco Cuccia, Ciro Franzese, Serena Badellino, Paolo Borghetti, Manuela Federico, Giulia Marvaso, Giampaolo Montesi, Antonio Pontoriero, Giuseppe Ferrera, Filippo Alongi, Marta Scorsetti","doi":"10.1007/s10585-024-10304-3","DOIUrl":"10.1007/s10585-024-10304-3","url":null,"abstract":"<p><strong>Background: </strong>The Study Group for the Biology and Treatment of the OligoMetastatic Disease on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) has conducted a national survey with the aim to depict the current patterns of practice of stereotactic body radiotherapy (SBRT) for spinal oligometastases.</p><p><strong>Methods: </strong>The Surveymonkey platform was used to send a 28-items questionnaire focused on demographic, clinical and technical aspects related to SBRT for spinal oligometastases. All the AIRO members were invited to fill the questionnaire. Data were then centralized to a single center for analysis and interpretation.</p><p><strong>Results: </strong>53 radiation oncologists from 47 centers fulfilled the survey. A complete agreement was observed in proposing SBRT for spinal oligometastases, with the majority considering up to 3 concurrent spine oligometastases feasible for SBRT (73.5%), regardless of spine site (70%), vertebral segment (85%) and morphological features of the lesion (71.7%). Regarding dose prescription, fractionated regimens resulted as the preferred option, either in 3 (58.4%) or five sessions (34%), with a substantial agreement in applying a PTV-margin larger than 1 mm (almost 90% of participants), and ideally using both MRI and PET imaging to improve target volume and organs-at-risk delineation (67.9%).</p><p><strong>Conclusions: </strong>This national italian survey illustrates the patterns of practice and the main issues for the indication of SBRT for spinal oligometastases. A substantial agreement in the numerical cut-off and vertebral segment involved for SBRT indication was reported, with a slight heterogeneity in terms of dose prescription and fractionation schemes.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"679-685"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A clinical-radiomics nomogram based on spectral CT multi-parameter images for preoperative prediction of lymph node metastasis in colorectal cancer.","authors":"Qian Li, Rui Hong, Ping Zhang, Liting Hou, Hailun Bao, Lin Bai, Jian Zhao","doi":"10.1007/s10585-024-10293-3","DOIUrl":"10.1007/s10585-024-10293-3","url":null,"abstract":"<p><p>To develop a clinical-radiomics nomogram based on spectral CT multi-parameter images for predicting lymph node metastasis in colorectal cancer. A total of 76 patients with colorectal cancer and 156 lymph nodes were included. The clinical data of the patients were collected, including gender, age, tumor location and size, preoperative tumor markers, etc. Three sets of conventional images in the arterial, venous, and delayed phases were obtained, and six sets of spectral images were reconstructed using the arterial phase spectral data, including virtual monoenergetic images (40 keV, 70 keV, 100 keV), iodine density maps, iodine no water maps, and virtual non-contrast images. Radiomics features of lymph nodes were extracted from the above images, respectively. Univariate analysis and least absolute shrinkage and selection operator (LASSO) regression were used to select features. A clinical model was constructed based on age and carcinoembryonic antigen (CEA) levels. The radiomics features selected were used to generate a composed radiomics signature (Com-RS). A nomogram was developed using age, CEA, and the Com-RS. The models' prediction efficiency, calibration, and clinical application value were evaluated by the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis, respectively. The nomogram outperforms the clinical model and the Com-RS (AUC = 0.879, 0.824). It is well calibrated and has great clinical application value. This study developed a clinical-radiomics nomogram based on spectral CT multi-parameter images, which can be used as an effective tool for preoperative personalized prediction of lymph node metastasis in colorectal cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"639-653"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stanley P Leong, S David Nathanson, Jonathan S Zager
{"title":"Correction to: Editorial: Cancer metastasis through the lymphovascular system: molecular mechanisms of cancer metastasis.","authors":"Stanley P Leong, S David Nathanson, Jonathan S Zager","doi":"10.1007/s10585-024-10287-1","DOIUrl":"10.1007/s10585-024-10287-1","url":null,"abstract":"","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"807-808"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Predictive value of 18 F-FDG PET/CT versus bone marrow biopsy and aspiration in pediatric neuroblastoma.","authors":"Zhenzhen Zhao, Chao Yang","doi":"10.1007/s10585-024-10295-1","DOIUrl":"10.1007/s10585-024-10295-1","url":null,"abstract":"","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":" ","pages":"809-811"},"PeriodicalIF":4.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}