دورية أكاديمية
أعرض في EDS

Adipocyte-conditioned medium induces resistance of breast cancer cells to lapatinib.

التفاصيل البيبلوغرافية
العنوان: Adipocyte-conditioned medium induces resistance of breast cancer cells to lapatinib.
المؤلفون: Geneste A; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Duong MN; Department of Oncology, Lausanne University Hospital Center (CHUV) and University of Lausanne, Epalinges, Switzerland., Molina L; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Conilh L; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France. conilh.louise@gmail.com., Beaumel S; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Cleret A; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Chettab K; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Lachat M; Hospices Civils de Lyon, Banque de tissus et cellules, 5 place d'Arsonval, 69003, Lyon, France., Jordheim LP; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Matera EL; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France., Dumontet C; Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM UMR 1052, CNRS 5286, 8 Avenue Rockefeller, 69008, Lyon, France.; Hospices Civils de Lyon, Services d'Hématologie, 165 Chemin du Grand Revoyet, 69310, Pierre-Bénite, France.
المصدر: BMC pharmacology & toxicology [BMC Pharmacol Toxicol] 2020 Aug 14; Vol. 21 (1), pp. 61. Date of Electronic Publication: 2020 Aug 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101590449 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-6511 (Electronic) Linking ISSN: 20506511 NLM ISO Abbreviation: BMC Pharmacol Toxicol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central
مواضيع طبية MeSH: Adipocytes* , Culture Media, Conditioned* , Drug Resistance, Neoplasm*, Antineoplastic Agents/*pharmacology , Breast Neoplasms/*drug therapy , Lapatinib/*pharmacology , Protein Kinase Inhibitors/*pharmacology, Animals ; Cell Cycle/drug effects ; Cell Line ; Female ; Humans ; Mice, SCID
مستخلص: Background: The existence of a cross-talk between peritumoral adipocytes and cancer cells has been increasingly investigated. Several studies have shown that these adipocytes protect tumor cells from the effect of anticancer agents.
Methods: To investigate a potential protective effect of adipocyte-conditioned medium on HER2 positive breast cancer cells exposed to tyrosine kinase inhibitors (TKI) such as lapatinib, we analyzed the sensitivity of HER2 positive breast cancer models in vitro and in vivo on SCID mice in the presence or absence of adipocytes or adipocyte-conditioned medium.
Results: Conditioned medium from differentiated adipocytes reduced the in vitro sensitivity of the HER2+ cell lines BT474 and SKBR3 to TKI. Particularly, conditioned medium abrogated P27 induction in tumor cells by lapatinib but this was observed only when conditioned medium was present during exposure to lapatinib. In addition, resistance was induced with adipocytes derived from murine NIH3T3 or human hMAD cells but not with fibroblasts or preadipocytes. In vivo studies demonstrated that the contact of the tumors with adipose tissue reduced sensitivity to lapatinib. Soluble factors involved in this resistance were found to be thermolabile. Pharmacological modulation of lipolysis in adipocytes during preparation of conditioned media showed that various lipolysis inhibitors abolished the protective effect of conditioned media on tumor cells, suggesting a role for adipocyte lipolysis in the induction of resistance of tumor cells to TKI.
Conclusions: Overall, our results suggest that contact of tumor cells with proximal adipose tissue induces resistance to anti HER2 small molecule inhibitors through the production of soluble thermolabile factors, and that this effect can be abrogated using lipolysis inhibitors.
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معلومات مُعتمدة: INCa_INSERM_DGOS_12563 International INCA (FR); PLBIO 2013-106 International INCA (FR)
فهرسة مساهمة: Keywords: Adipocytes; Breast cancer; HER2; Lapatinib; Resistance
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Culture Media, Conditioned)
0 (Protein Kinase Inhibitors)
0VUA21238F (Lapatinib)
تواريخ الأحداث: Date Created: 20200816 Date Completed: 20210702 Latest Revision: 20210702
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7427918
DOI: 10.1186/s40360-020-00436-z
PMID: 32795383
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-6511
DOI:10.1186/s40360-020-00436-z