Diminished metastasis in tetraspanin CD151-knockout mice.

Tetraspanin protein CD151 on tumor cells supports invasion and metastasis. In the present study, we show that host animal CD151 also plays a critical role. CD151-null mice showed markedly diminished experimental lung metastasis after injection of Lewis lung carcinoma or B16F10 melanoma cells.

Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo.

EWI-2, a cell surface IgSF protein, is highly expressed in normal human brain but is considerably diminished in glioblastoma tumors and cell lines. Moreover, loss of EWI-2 expression correlated with a shorter survival time in human glioma patients, suggesting that EWI-2 might be a natural inhibitor of glioblastoma. In support of this idea, EWI-2 expression significantly impaired both ectopic and orthotopic tumor growth in nude mice in vivo.

CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization.

CD151, a master regulator of laminin-binding integrins (alpha(6)beta(4), alpha(6)beta(1), and alpha(3)beta(1)), assembles these integrins into complexes called tetraspanin-enriched microdomains. CD151 protein expression is elevated in 31% of human breast cancers and is even more elevated in high-grade (40%) and estrogen receptor-negative (45%) subtypes. The latter includes triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) basal-like tumors.

Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro.

Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed no vascular defects during normal development or during neonatal oxygen-induced retinopathy.

Tetraspanin CD151 regulates alpha6beta1 integrin adhesion strengthening.

The tetraspanin CD151 molecule associates specifically with laminin-binding integrins, including alpha6beta1. To probe strength of alpha6beta1-dependent adhesion to laminin-1, defined forces (0-1.5 nN) were applied to magnetic laminin-coated microbeads bound to NIH 3T3 cells.

An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology.

The alpha 3 beta 1 integrin shows strong, stoichiometric, direct lateral association with the tetraspanin CD151. As shown here, an extracellular CD151 site (QRD(194-196)) is required for strong (i.e.

Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis.

Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-alpha6beta1 integrin antibodies. For NIH3T3 cells transfected with human CD151 protein, the formation of a cord-like network was also inhibitable by anti-CD151 antibodies. Furthermore, CD151 and alpha6beta1 were physically associated within NIH3T3 cells.