Functional heterogeneity of non-small lung adenocarcinoma cell sub-populations.

The morphological and functional heterogeneity of solid tumour cells can be observed in cancer cell lines cultured in vitro. We have combined analyses of microclones developed from single cells with micropore transmigration assays to demonstrate the co-existence of cellular subsets differing in morphology and motile activity, as well as Cx43 (connexin 43) and N-cadherin expression within lung carcinoma A549 populations. 'Fibroblastoid' cells, characterized by high motility, polarized morphology and plasmalemmal localization of Cx43, displayed the strongest aptitude for transmigration through narrow obstacles.

DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of Cx43.

The formation of aqueous intercellular channels mediating gap junctional intercellular coupling (GJIC) is a canonical function of connexins (Cx). In contrast, mechanisms of GJIC-independent involvement of connexins in cancer formation and metastasis remain a matter of debate. Because of the role of Cx43 in the determination of carcinoma cell invasive potential, we addressed the problem of the possible Cx43 involvement in early prostate cancer invasion.

Blood monocytes stimulate migration of human pancreatic carcinoma cells in vitro: the role of tumour necrosis factor - alpha.

In some types of cancers, tumour-infiltrating monocytes/macrophages (TIM) may be responsible for the formation of an invasive microenvironment in a manner dependent on the secretion of soluble mediators such as tumour necrosis factor-alpha (TNF). Human pancreatic carcinoma (HPC-4) cells are able to induce TNF production by monocytes. Here, the effect of human peripheral blood monocytes, precursors of TIM, on the motility of co-cultured HPC-4 cells, was directly analysed in vitro.

Cell motility affects the intensity of gap junctional coupling in prostate carcinoma and melanoma cell populations.

Connexins and gap junctions play a crucial role during carcinogenesis. While diverse regulatory systems have been shown to modulate their function, the influence of cell motility on the intensity of gap junctional intercellular coupling has yet to be systematically addressed. Since cancer cell motility and intercellular coupling determine cancer development, we aimed at elucidating how mutual cell translocation modulates the intensity of gap junctional coupling in cell populations.

Hemostatic effects of recombinant DisBa-01, a disintegrin from Bothrops alternatus.

A monomeric RGD-disintegrin was recently identified from a cDNA library from the venom gland of Bothrops alternatus. The corresponding 12 kDa-recombinant protein, DisBa-01, specifically interacted with alpha(v)beta3 integrin and displayed potent anti-metastatic and anti-angiogenic properties. Here, the interaction of DisBa-01 with platelet alphaIIb beta3 integrin and its effects on hemostasis and thrombosis were investigated.

A novel alpha(v)beta (3)-blocking disintegrin containing the RGD motive, DisBa-01, inhibits bFGF-induced angiogenesis and melanoma metastasis.

The integrin alpha(v)beta(3) is involved in multiple aspects of malignant cancer, including tumor angiogenesis and metastasis, which makes the receptor a key target for the development of anti-cancer therapies. We report here on the production, the characterization and the in vivo anti-angiogenic and anti-metastatic properties of a novel alpha(v)beta(3)-binding disintegrin, DisBa-01, isolated from a cDNA library made with RNAs from the venom gland of Bothrops alternatus. The 11,637 Da-recombinant monomeric form of DisBa-01 displayed an RGD motif and interacted with purified alpha(v)beta(3) integrin in surface plasmon resonance studies, in a dose-dependent and cation sensitive manner.