Cancer Cells Cue the p53 Response of Cancer-Associated Fibroblasts to Cisplatin
| العنوان: | Cancer Cells Cue the p53 Response of Cancer-Associated Fibroblasts to Cisplatin |
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| المؤلفون: | Jens O Schmid, Walter E. Aulitzky, Silke Haubeiss, Heiko van der Kuip, Sabine Bode, German Ott, Moshe Oren, Godehard Friedel, Meng Dong, Thomas E. Mürdter, Andreas Grabner |
| المصدر: | Cancer Research. 72:5824-5832 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, Cell type, Lung Neoplasms, Cell, Antineoplastic Agents, Biology, Tissue culture, Tumor Microenvironment, medicine, Humans, Lung cancer, Cisplatin, Tumor microenvironment, Fibroblasts, medicine.disease, Immunohistochemistry, Ki-67 Antigen, medicine.anatomical_structure, Oncology, Cancer cell, Cancer research, Cancer-Associated Fibroblasts, Tumor Suppressor Protein p53, DNA Damage, medicine.drug |
| الوصف: | Current understanding of the p53 response is based mainly upon in vitro studies of homogeneous cell populations. However, there is little information on whether the same principles operate within heterogeneous tumor tissues that are comprised of cancer cells and other cell types, including cancer-associated fibroblasts (CAF). Using ex-vivo tissue cultures, we investigated p53 status and responses to cisplatin in tumor cells and CAFs from tissue specimens isolated from 32 lung cancer patients. By comparing cultivated tissue slices with the corresponding tumor tissues fixed immediately after surgery, we found that morphology, proliferation, and p53 staining pattern were preserved during cultivation. Unexpectedly, when CAFs were analyzed, p53 accumulation and induction of p21 was observed only in tumors with constitutively low p53 protein and accumulation upon cisplatin treatment. In contrast, in tumors with no p53 accumulation in cancer cells there was also no p53 accumulation or p21 induction in adjacent CAFs. Furthermore, induction of cisplatin-induced apoptosis in CAFs was selectively observed in tumors characterized by a parallel induction of cancer cell death. Our findings reveal an interdependence of the p53 response in cancer cells and adjacent CAFs within tumor tissues, arguing that cancer cells control the response of their microenvironment to DNA damage. Cancer Res; 72(22); 5824–32. ©2012 AACR. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82a5419329da87758e648a729085ec66 https://doi.org/10.1158/0008-5472.can-12-1201 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....82a5419329da87758e648a729085ec66 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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