NDLI: Tetraspanin CD151 regulates growth of mammary epithelial cells in 3-D ECM: implication for mammary DCIS

Content Provider	PubMed Central
Author	Vera, Novitskaya Hanna, Romanska Dawoud, Marwa Jones, J. Louise Fedor, Berditchevski
Abstract	Tetraspanin CD151 is associated with laminins-binding integrins (i.e. α3β1, α6β1 and α6β4) and regulates tumour cell migration and invasion. Here we examined the role of CD151 in proliferation of mammary epithelial cells using in vitro and in vivo models. Depletion of CD151 suppressed growth of HB2 cells, a non-tumourigenic breast epithelial cell line, in 3-D extracellular matrices (ECM) and in Matrigel-based xenografts. Whilst the presence of α3β1 (but not α6 integrins) was necessary to support growth of HB2 cells in 3-D ECM, the pro-proliferative activity of CD151 did not require the direct interaction with integrins. Furthermore, depletion of CD151 potentiated formation of the internal lumen and partial restoration of polarity when HB2 cells were cultured in 3-D ECM. This correlated with a decrease in phosphorylation levels of Erk1/2 and cAkt in CD151-negative cells and increase in activation of Caspase-3. Accordingly, the number of CD151-positive colonies with internal lumen was increased by approximately five-fold when cells were cultured in the presence of MEK (U0126) and PI3-K (LY29004) inhibitors. To establish physiological relevance of pro-proliferative and morphogenetic activities of CD151 we analysed expression of this tetraspanin in ductal carcinoma in situ (DCIS), which is characterized by neoplastic proliferation of mammary epithelial cells. Strong homogeneous membrane expression of CD151 was found to be associated with high grade of DCIS (p=0.004). Taken together these results strongly suggest that CD151 complexes play a crucial role in the development of hyperproliferative diseases in the mammary gland.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-09-4330
Ending Page	4708
Page Count	11
Starting Page	4698
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	11
Volume Number	70
Language	English
Publisher Date	2010-06-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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