Article

The Inhibition of Tumor Cell Intravasation and Subsequent Metastasis via Regulation of In Vivo Tumor Cell Motility by the Tetraspanin CD151

Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cancer cell (Impact Factor: 23.89). 04/2008; 13(3):221-34. DOI: 10.1016/j.ccr.2008.01.031
Source: PubMed

ABSTRACT In vivo tumor cell migration through integrin-dependent pathways is key to the metastatic behavior of malignant cells. Using quantitative in vivo assays and intravital imaging, we assessed the impact of cell migration, regulated by the integrin-associated tetraspanin CD151, on spontaneous human tumor cell metastasis. We demonstrate that promoting immobility through a CD151-specific metastasis blocking mAb prevents tumor cell dissemination by inhibiting intravasation without affecting primary tumor growth, tumor cell arrest, extravasation, or growth at the secondary site. In vivo, this loss of migration is the result of enhanced tumor cell-matrix interactions, promoted by CD151, which prevent dissociation by individual cells and leads to a subsequent inhibition of invasion and intravasation at the site of the primary tumor.

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Available from: Andries Zijlstra, Aug 25, 2015
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    • "The initial evidence that CD151 promotes metastasis came from a study showing that a monoclonal antibody with unknown specificity inhibited metastasis by a human epidermoid carcinoma line in vivo. This antibody inhibited cell migration without affecting adhesion or proliferation [47] [48]. Overexpression of CD151 has also been associated with poor prognosis in HCC and potentiates the metastatic behaviour of cancerous cells [49]. "
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    • "The initial evidence that CD151 promotes metastasis came from a study showing that a monoclonal antibody with unknown specificity inhibited metastasis by a human epidermoid carcinoma line in vivo. This antibody inhibited cell migration without affecting adhesion or proliferation [47] [48]. Overexpression of CD151 has also been associated with poor prognosis in HCC and potentiates the metastatic behaviour of cancerous cells [49]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As in many tumors, heterogeneity within the cell population is one of the main features of hepatocellular carcinoma (HCC). Heterogeneity results from the ability of tumor to produce multiple subpopulations of cells with diverse genetic, biochemical and immunological characteristics. Little is known about how heterogeneity emerges and how it is maintained. Fluctuations in single cells can be masked or completely misrepresented when cell populations are analyzed. It has become exceedingly apparent that the utility of measurement based on the analysis of bulk specimens is limited by intra-tumor genetic and epigenetic heterogeneity, as characteristics of the most abundant cell type might not necessarily predict the properties of cell populations. Yet, such non-uniformities often unveil molecular patterns that can represent mechanisms of tumor progression. Interestingly, variability among single cells in a population may arise from different responses to intrinsic and extrinsic perturbations mainly mediated by the plasma membrane. The association of certain proteins, including tetraspanins, and lipids in specific location on the plasma membrane constitutes specialized structure called tetraspanin-enriched microdomains (TEMs). TEMs organization in cancer may reveal essential clues for understanding pathogenic mechanisms underlying cancer progression. Along these lines, TEMs and HCC progression represent a valuable paradigm for gaining a deeper understanding of such mechanisms.
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