CD63: is it pro-metastatic or anti-metastatic?

Fri, 09/18/2015 - 13:04

CD63 is a type II membrane protein belonging to tetraspanin superfamily and it play key roles in the activation of several cellular signaling cascades along with acting as TIMP1 receptor. It is expressed by activated platelets, monocytes, macrophages, granulocytes, T /B cells, and different type of cancer cells. CD63 localizes to endosomes, lysosomes and on the cellular surfaces, and is often considered as a marker for late endosomes as well as for lysosomes. Besides its major role in regulation of intracellular transport and localization of several proteins, CD63 controls several processes such as cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration (1). Moreover, CD63 plays an essential role during HIV-1 replication and it has been shown to incorporate into HIV-1 virions, and to colocalize with HIV-1 Env and Gag proteins in HIV-1 producing cells (2). Most of the recent studies on CD63 has been focused on its role in cancer development/metastasis because it is, so far, the only known membrane receptor which directly interacts with TIMP-1, the endogenous inhibitor of most secreted MMPs as well as the membrane-bound metalloproteinase ADAM-10.

CD63 Antibody (H5C6) [NBP2-42225] - Immunocytochemistry/Immunofluorescence analysis of HeLa cells using CD63 antibody (clone H5C6) at a 1:50 dilution followed by detection employing Dylight 488 –labelled anti-Mouse secondary antibody (Green). Actin and nuclei were counterstained against Phalloidin 568 (Red) and DAPI (Blue), respectively.

CD63 is known to be upregulated in breast cancer, astrocytoma, melanoma etc. and many of the initial studies suggested it as tumor suppressor. Interestingly, it is highly expressed during the early stages of melanoma, while decreasing in advanced stages wherein it was recently reported to downregulate the invasive/metastatic potential of melanoma cancer cells via suppression of epithelial-to-mesenchymal transition (EMT) markers such as N-cadherin, Vimentin, Zeb1 and alpha-SMA (3). Contrastingly, in ovarian carcinoma cell line SKOV3ipL, CD63 knock down lead to enhanced epithelial-like phenotype with concomitant increase in E-cadherin and downregulation of EMT markers namely Slug, Zeb1, N-cadherin, beta-catenin, MMP-2 and PAI-1 (4). Additional studies are warranted on CD63 protein with reference to its potential differential effects on the invasive/metastatic properties of different type of cancer cells.

Novus Biologicals offers a variety of high quality CD63 products for your research needs including: CD63 Antibodies, Lysates, and Proteins and Peptides


  1. Pols and Klumperman (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res.  315 (9):1584-92.
  2. Fu et al (2015) Tetraspanin CD63 is a regulator of HIV-1 replication. Int J Clin Exp Pathol. 8(2):1184-98.
  3. Lupia et al (2014) CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells. J Invest Dermatol.  134 (12):2947-56.
  4. Seubert et al (2015) Tetraspanin CD63 acts as a pro-metastatic factor via β-catenin stabilization. Int J Cancer. 136(10):2304-15.

By: Subhash Gangar

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