Tumor Biology最新文献

{"title":"Abstract 2837: NR2F1 is a barrier to early dissemination of pre-malignant mammary cells","authors":"M. Sosa, Carolina Rodriguez-Tirado, Nupura Kale, M. Carlini, N. Shrivastava, Bassem D. Khalil, J. Bravo-Cordero, Melissa Alexander, Jiayi Ji","doi":"10.1158/1538-7445.AM2021-2837","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2837","url":null,"abstract":"Cancer cells disseminate during very early and sometimes asymptomatic stages of tumor progression. Granted that biological barriers to tumorigenesis exist, there must also be limiting steps to early dissemination, all of which remain largely unknown. We report that the orphan nuclear receptor NR2F1/COUP-TF1 serves as a barrier to early dissemination. High-resolution intravital imaging revealed that loss of function of NR2F1 in HER2+ early cancer cells increased in vivo dissemination without accelerating mammary tumor formation. NR2F1 expression was positively regulated by the tumor suppressive MMK3/6-p38-MAPK pathway and downregulated by HER2 and Wnt4 oncogenic signaling. NR2F1 downregulation by HER2 in early cancer cells led to decreased E-cadherin expression and β-catenin membrane localization, disorganized laminin 5 deposition, and increased expression of CK14, TWIST1, ZEB1 and PRRX1. Our findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 downstream of HER2 signaling. Citation Format: Maria Soledad Sosa, Carolina Rodriguez-Tirado, Nupura Kale, Maria Carlini, Nitisha Shrivastava, Bassem Khalil, Javier Bravo-Cordero, Melissa Alexander, Jiayi Ji. NR2F1 is a barrier to early dissemination of pre-malignant mammary cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2837.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42565653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2964: Immuno-reactive cancer organoid models to examine microbiome metabolite effects on immune checkpoint blockade efficacy","authors":"Ethan Shelkey, D. Soto-Pantoja, Yong Lu, S. Soker","doi":"10.1158/1538-7445.AM2021-2964","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2964","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42603333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2918: Characterization of a novel transplantable C3TAg breast cancer model in C57BL/6J mice","authors":"Meredith S. Carson, Michael F. Colman, Daniel Roth, Jody E. Albright, Melissa A. VerHague, J. French, S. Hursting","doi":"10.1158/1538-7445.AM2021-2918","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2918","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42658739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2658: Oncogenicity of adeno-associated virus (AAV) integration into the genomes of liver cancer patients depends on the overlap between the AAV integration site and the AAV X gene","authors":"A. Schäffer, D. Dominguez, E. Gertz, Lesley M. Chapman, A. Budhu, M. Forgues, Jittiporn Chaisaingmongkol, S. Rabibhadana, Benjarath Pupacdi, Xiaolin Wu, C. Harris, M. Ruchirawat, E. Ruppin, X. Wang","doi":"10.1158/1538-7445.AM2021-2658","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2658","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42728087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2661: Role of NKX2-1 in thyroid neoplasms induced by iodine-deficiency and radiation","authors":"Yo-taro Shirai, Yoshinori Takizawa, M. Iwadate, Jorge Paiz, Shigetoshi Yokoyama, Masaaki Miyakoshi, J. Ward, S. Kimura","doi":"10.1158/1538-7445.AM2021-2661","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2661","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47882084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 3120: MMP-7 increases migration by decreasing intercellular cell junction complexes in prostate cancer microtumors formed by perlecan/HSPG2","authors":"Lissette A. Cruz, Tristen V. Tellman, O. Igoshin, D. Carson, M. Farach-Carson","doi":"10.1158/1538-7445.AM2021-3120","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3120","url":null,"abstract":"Background: Polarized epithelium is stabilized by lateral cell-cell interactions via cell adhesion molecules (CAMs) and by cell-matrix interactions with basement membrane including with perlecan/HSPG2 (pln). Prostate cancer (PCa) patients with bone metastases have circulating pln fragments, with inverse correlation between MMP-7 staining and loss of pln in cancer tissue. Cleavage of pln by MMP-7 increases cell-matrix interactions and dysregulates cell signaling, permitting migration. We earlier showed pln domain IV-3 (DmIV-3) drives cell-cell cohesion and, when digested with MMP-7, drives cell dyscohesion. Methods: To evaluate the impact of MMP-7 and pln fragments on microtumor dyscohesion and cell migration, uniformly sized PCa microtumors were pre-formed in a microwell system. Pre-formed microtumors were transferred to Dm IV-3 or full length perlecan (FL pln) coated wells for 16-24 hrs. Microtumors were treated with MMP-7 alone or MMP-7 plus predigested Dm IV-3 fragments or MMP-7 plus FL pln fragments. For live cell imaging, tracking of migratory cells leaving microtumors was performed with Imaris software. Co-location of cell adhesion complex components was assessed with Imaris Spots. Results: Pre-formed microtumors cultured with DmIV-3 cleaved by MMP-7 showed lower Pearson9s correlation values at cell boundaries compared to microtumors treated with intact Dm IV-3. Line scan analysis revealed E-cadherin and F-actin fluorescent signals were enriched and co-aligned in microtumors treated with Dm IV-3; enrichment and co-alignment were reduced when DmIV-3 fragments and MMP-7 were present. Track number detected per cell cluster was highest in the presence of FL pln fragments plus MMP-7 along with a measurable change in distribution of track displacement lengths of cells toward high values. Conclusion: Boundary reorganization promotes a migratory cell phenotype in microtumors treated with MMP-7 and DmIV-3 fragments. DmIV-3 fragments generated by MMP-7 cleavage can enhance cell dyscohesion by disrupting interactions between CAMs. Ongoing work will identify DmIV-3 fragment(s) positively associated with tumor dyscohesion that play key roles in secondary metastasis formation. Following patterns of dyscohesion of pre-formed microtumors provides a good model to study dynamic changes in intercellular junction components and quantitate cell migration patterns that foster circulating tumor cell formation and metastasis. Citation Format: Lissette A. Cruz, Tristen V. Tellman, Oleg Igoshin, Daniel Carson, Mary (Cindy) Farach-Carson. MMP-7 increases migration by decreasing intercellular cell junction complexes in prostate cancer microtumors formed by perlecan/HSPG2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3120.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48107168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 3191: The effect of metformin on the tumor immune microenvironment","authors":"A. Saito, H. Ohzawa, Yuki Kaneko, Kohei Tamura, Yurie Futoh, Kazuya Takahashi, Y. Kimura, Mineyuki Tojo, Y. Kumagai, H. Miyato, N. Sata, J. Kitayama","doi":"10.1158/1538-7445.AM2021-3191","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3191","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48265400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 3013: Orthotopic patient-derived xenografts (O-PDX) are effective precision oncology models that can predict therapeutic response, recurrence, and acquired drug resistance","authors":"J. Nakashima, Jantzen Sperry, Bianca Carapia, D. Yan, A. Chin, A. Shahsafaei, Joan W Chen, Yuan-hung Chien, Christophe Pedros, N. Federman, Arun D. Singh, F. Eilber, B. Datnow","doi":"10.1158/1538-7445.AM2021-3013","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3013","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43087997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2747: Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer","authors":"I.-M. Launonen, N. Lyytikäinen, J. Casado, Ella Anttila, C. Jacobson, Jia-Ren Lin, Z. Maliga, Sandro Santaga, K. Elias, A. D’Andrea, P. Konstantinopoulos, P. Sorger, A. Färkkilä","doi":"10.1158/1538-7445.AM2021-2747","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2747","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 3159: Targeting the TGFΒ/TIMP-1/2 axes to re-educate pro-inflammatory/pro angiogenic NK cells in cancer patients","authors":"M. Gallazzi, A. Bruno, D. Noonan, W. Stetler-Stevenson, A. Albini","doi":"10.1158/1538-7445.AM2021-3159","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3159","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45702200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}