The Collagen Receptor Endo180 (CD280) Is Expressed on Basal-like Breast Tumor Cells and Promotes Tumor Growth In vivo
| العنوان: | The Collagen Receptor Endo180 (CD280) Is Expressed on Basal-like Breast Tumor Cells and Promotes Tumor Growth In vivo |
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| المؤلفون: | Gareth C. Davies, Jorge S. Reis-Filho, Clare M. Isacke, Andrew R. Green, David Robertson, Justin Sturge, Damian A. Johnson, Maryou B K Lambros, Dirk Wienke, Kay Savage, Ian O. Ellis, Somaia Elsheikh |
| المصدر: | Cancer Research. 67:10230-10240 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Cancer Research, Pathology, medicine.medical_specialty, CD30, Breast Neoplasms, Tumor M2-PK, Biology, Collagen receptor, Extracellular matrix, Mice, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Receptor, Mice, Inbred BALB C, Cell migration, Transfection, Gene Expression Regulation, Neoplastic, Oncology, Tissue Array Analysis, Cell culture, Receptors, Mitogen, Cancer research, Female |
| الوصف: | Tumor cell invasion into the surrounding stroma requires increased cell motility and extensive remodeling of the extracellular matrix. Endo180 (CD280, MRC2, urokinase-type plasminogen activator receptor-associated protein) is a recycling endocytic receptor that functions in both these cellular activities by promoting cell migration and uptake of collagens for intracellular degradation. In the normal breast, Endo180 is predominantly expressed by stromal fibroblasts. The contrary observation that Endo180 is expressed on epithelial tumor cell lines that display a high invasive capacity suggested that up-regulation of this receptor may be an associated and functional component in the acquisition of a more aggressive phenotype by tumor cells in vivo. Here, we show that high levels of Endo180 are found in a subset of basal-like breast cancers and that this expression is an independent prognostic marker for shorter disease-free survival. Two potential mechanisms for Endo180 up-regulation were uncovered. First, it was shown that Endo180 can be transcriptionally up-regulated in vitro following transforming growth factor-β treatment of breast cancer cells. Second, a proportion of Endo180+ tumors were shown to have Endo180 gene copy number gains and amplifications. To investigate the functional consequence of Endo180 up-regulation, MCF7 cells transfected with Endo180 were inoculated into immunocompromised mice. Expression of wild-type Endo180, but not an internalization-defective Endo180 mutant, resulted in enhanced tumor growth together with a reduction in tumor collagen content. Together, these data argue that elevated expression of this receptor in tumor cells could have important consequences in subsets of basal-like carcinomas for which there is a current lack of effective treatment. [Cancer Res 2007;67(21):10230–11] |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-06-3496 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c47d2af475f446536e2d709769d3bf75 https://doi.org/10.1158/0008-5472.can-06-3496 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c47d2af475f446536e2d709769d3bf75 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/0008-5472.can-06-3496 |