دورية أكاديمية
أعرض في EDS

Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts.

التفاصيل البيبلوغرافية
العنوان: Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts.
المؤلفون: Sotgia F; Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10 Street, Philadelphia, PA 19107, USA. federica.sotgia@jefferson.edu, Del Galdo F, Casimiro MC, Bonuccelli G, Mercier I, Whitaker-Menezes D, Daumer KM, Zhou J, Wang C, Katiyar S, Xu H, Bosco E, Quong AA, Aronow B, Witkiewicz AK, Minetti C, Frank PG, Jimenez SA, Knudsen ES, Pestell RG, Lisanti MP
المصدر: The American journal of pathology [Am J Pathol] 2009 Mar; Vol. 174 (3), pp. 746-61.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0370502 Publication Model: Print Cited Medium: Internet ISSN: 1525-2191 (Electronic) Linking ISSN: 00029440 NLM ISO Abbreviation: Am J Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2011-: New York : Elsevier
Original Publication: Philadelphia [etc.] American Assn. of Pathologists [etc.]
مواضيع طبية MeSH: Breast Neoplasms/*genetics , Breast Neoplasms/*pathology , Caveolin 1/*deficiency , Caveolin 1/*genetics , Fibroblasts/*pathology , Stromal Cells/*pathology, Blotting, Western ; Breast/cytology ; Breast/physiology ; Breast Neoplasms/mortality ; Cell Culture Techniques ; Cell Division ; Disease Progression ; Disease-Free Survival ; Epithelial Cells/cytology ; Epithelial Cells/pathology ; Epithelial Cells/physiology ; Female ; Fibroblasts/cytology ; Fibroblasts/physiology ; Humans ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Stromal Cells/cytology ; Stromal Cells/physiology ; Survival Analysis
مستخلص: Recently, we reported that human breast cancer-associated fibroblasts show functional inactivation of the retinoblastoma (RB) tumor suppressor and down-regulation of caveolin-1 (Cav-1) protein expression. However, it remains unknown whether loss of Cav-1 is sufficient to confer functional RB inactivation in mammary fibroblasts. To establish a direct cause-and-effect relationship, mammary stromal fibroblasts (MSFs) were prepared from Cav-1(-/-) null mice and subjected to phenotypic analysis. Here, we provide evidence that Cav-1(-/-) MSFs share many characteristics with human cancer-associated fibroblasts. The Cav-1(-/-) MSF transcriptome significantly overlaps with human cancer-associated fibroblasts; both show a nearly identical profile of RB/E2F-regulated genes that are up-regulated, which is consistent with RB inactivation. This Cav-1(-/-) MSF gene signature is predictive of poor clinical outcome in breast cancer patients treated with tamoxifen. Consistent with these findings, Cav-1(-/-) MSFs show RB hyperphosphorylation and the up-regulation of estrogen receptor co-activator genes. We also evaluated the paracrine effects of "conditioned media" prepared from Cav-1(-/-) MSFs on wild-type mammary epithelia. Our results indicate that Cav-1(-/-) MSF "conditioned media" is sufficient to induce an epithelial-mesenchymal transition, indicative of an invasive phenotype. Proteomic analysis of this "conditioned media" reveals increased levels of proliferative/angiogenic growth factors. Consistent with these findings, Cav-1(-/-) MSFs are able to undergo endothelial-like transdifferentiation. Thus, these results have important implications for understanding the role of cancer-associated fibroblasts and RB inactivation in promoting tumor angiogenesis.
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معلومات مُعتمدة: R01 CA075503 United States CA NCI NIH HHS; R01 CA098779 United States CA NCI NIH HHS; R01-CA-120876 United States CA NCI NIH HHS; R01 CA120876 United States CA NCI NIH HHS; R01-CA-70896 United States CA NCI NIH HHS; R01-CA-098779 United States CA NCI NIH HHS; R01 CA070896 United States CA NCI NIH HHS; R01 CA107382 United States CA NCI NIH HHS; T32 CA117846 United States CA NCI NIH HHS; R01-CA-86072 United States CA NCI NIH HHS; R01-CA-80250 United States CA NCI NIH HHS; P30-CA-56036 United States CA NCI NIH HHS; R01-CA-107382 United States CA NCI NIH HHS; R01 AR055660 United States AR NIAMS NIH HHS; R01-CA-75503 United States CA NCI NIH HHS; R01 CA080250 United States CA NCI NIH HHS; R01 CA086072 United States CA NCI NIH HHS; R01 AR055660-03 United States AR NIAMS NIH HHS; P30 CA056036 United States CA NCI NIH HHS
المشرفين على المادة: 0 (CAV1 protein, human)
0 (Caveolin 1)
0 (RNA, Messenger)
0 (RNA, Neoplasm)
تواريخ الأحداث: Date Created: 20090224 Date Completed: 20090323 Latest Revision: 20211020
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC2665737
DOI: 10.2353/ajpath.2009.080658
PMID: 19234134
قاعدة البيانات: MEDLINE
الوصف
تدمد:1525-2191
DOI:10.2353/ajpath.2009.080658