Natalia M Weinzierl, Jayarani Putri, Kathryn M Spitler, Erin E Talbert
{"title":"胰腺癌诱导恶病质的KPP小鼠模型的性别特异性生存而非组织消耗。","authors":"Natalia M Weinzierl, Jayarani Putri, Kathryn M Spitler, Erin E Talbert","doi":"10.1152/japplphysiol.00706.2025","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer cachexia, a multifactorial condition resulting in muscle and adipose tissue wasting, reduces the quality of life of many people with cancer. Cachexia is highly prevalent in people with pancreatic ductal adenocarcinoma (PDAC), and many animal models of pancreatic cancer are used to understand mechanisms underlying cachexia. One such model is the <i>Kras<sub>LSL-G12D</sub></i>, <i>Ptf1a<sup>Cre-ER/+</sup></i>, <i>Pten<sup>flox/flox</sup></i> (KPP) model, which utilizes an inducible Cre recombinase to initiate tumor development by tamoxifen administration. In our previous work, tumors were induced in KPP mice at 4 weeks of age. However, mice are rapidly growing at this age, and a portion of the body weight differences seen between control and KPP mice is likely due to slowed growth of KPP mice. In our current study, pancreatic tumors were induced to develop with tamoxifen in KPP mice after rapid postnatal growth has slowed at 10 weeks of age (KPP10). Given the expanding evidence of sexual dimorphisms in cancer cachexia, we utilized both male and female mice to assess potential sex differences. Similar to our previous findings, KPP10 mice had lower body, muscle, and adipose tissue weights compared to non-tumor mice, and these differences were similar between male and female mice. However, male mice experienced greater relative weight loss. Unexpectedly, we identified that survival was significantly shorter in female KPP10 mice compared to KPP10 males. Greater body weight at tumor induction was associated with longer survival, suggesting that the sex difference in survival may be related to differences in body weight between male and female mice.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sex-specific survival but not tissue wasting in the KPP mouse model of pancreatic cancer-induced cachexia.\",\"authors\":\"Natalia M Weinzierl, Jayarani Putri, Kathryn M Spitler, Erin E Talbert\",\"doi\":\"10.1152/japplphysiol.00706.2025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer cachexia, a multifactorial condition resulting in muscle and adipose tissue wasting, reduces the quality of life of many people with cancer. Cachexia is highly prevalent in people with pancreatic ductal adenocarcinoma (PDAC), and many animal models of pancreatic cancer are used to understand mechanisms underlying cachexia. One such model is the <i>Kras<sub>LSL-G12D</sub></i>, <i>Ptf1a<sup>Cre-ER/+</sup></i>, <i>Pten<sup>flox/flox</sup></i> (KPP) model, which utilizes an inducible Cre recombinase to initiate tumor development by tamoxifen administration. In our previous work, tumors were induced in KPP mice at 4 weeks of age. However, mice are rapidly growing at this age, and a portion of the body weight differences seen between control and KPP mice is likely due to slowed growth of KPP mice. In our current study, pancreatic tumors were induced to develop with tamoxifen in KPP mice after rapid postnatal growth has slowed at 10 weeks of age (KPP10). Given the expanding evidence of sexual dimorphisms in cancer cachexia, we utilized both male and female mice to assess potential sex differences. Similar to our previous findings, KPP10 mice had lower body, muscle, and adipose tissue weights compared to non-tumor mice, and these differences were similar between male and female mice. However, male mice experienced greater relative weight loss. Unexpectedly, we identified that survival was significantly shorter in female KPP10 mice compared to KPP10 males. Greater body weight at tumor induction was associated with longer survival, suggesting that the sex difference in survival may be related to differences in body weight between male and female mice.</p>\",\"PeriodicalId\":15160,\"journal\":{\"name\":\"Journal of applied physiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of applied physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1152/japplphysiol.00706.2025\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of applied physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/japplphysiol.00706.2025","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Sex-specific survival but not tissue wasting in the KPP mouse model of pancreatic cancer-induced cachexia.
Cancer cachexia, a multifactorial condition resulting in muscle and adipose tissue wasting, reduces the quality of life of many people with cancer. Cachexia is highly prevalent in people with pancreatic ductal adenocarcinoma (PDAC), and many animal models of pancreatic cancer are used to understand mechanisms underlying cachexia. One such model is the KrasLSL-G12D, Ptf1aCre-ER/+, Ptenflox/flox (KPP) model, which utilizes an inducible Cre recombinase to initiate tumor development by tamoxifen administration. In our previous work, tumors were induced in KPP mice at 4 weeks of age. However, mice are rapidly growing at this age, and a portion of the body weight differences seen between control and KPP mice is likely due to slowed growth of KPP mice. In our current study, pancreatic tumors were induced to develop with tamoxifen in KPP mice after rapid postnatal growth has slowed at 10 weeks of age (KPP10). Given the expanding evidence of sexual dimorphisms in cancer cachexia, we utilized both male and female mice to assess potential sex differences. Similar to our previous findings, KPP10 mice had lower body, muscle, and adipose tissue weights compared to non-tumor mice, and these differences were similar between male and female mice. However, male mice experienced greater relative weight loss. Unexpectedly, we identified that survival was significantly shorter in female KPP10 mice compared to KPP10 males. Greater body weight at tumor induction was associated with longer survival, suggesting that the sex difference in survival may be related to differences in body weight between male and female mice.
期刊介绍:
The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.