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D Belotti

Publications and source records attributed to D Belotti.

23 records · Page 2Linked to original sources
PubMed1993

Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene.

Polyoma virus middle T-transformed murine endothelioma cell lines provide a useful model for studying vascular lesions such as hemangiomas, hemangiosarcomas, and Kaposi's sarcoma and tumor-associated angiogenesis. In vivo they produce fast-growing, hemorrhaging, cavernous blood-filled hemangiomas, mainly formed by recruited host endothelial cells, suggesting an angiogenesis-like process underlying the lesion. The molecular mechanism(s) responsible for the recruitment of host endothelial cells by endothelioma cells has not yet been identified. We found that five different cultured endothelioma cell lines produced a soluble factor, named endothelioma-derived motility factor (EDMF) that stimulates chemotaxis (motility induced by a gradient of soluble attractant), haptotaxis (motility in response to substrate-bound attractant), and chemoinvasion (migration through a layer of reconstituted basement membrane, Matrigel) of normal human, bovine, and murine endothelial cells. The inhibitory effect of actinomycin D and of enzymatic treatment on its activity proved that EDMF is a protein. EDMF binds to heparin, since its activity was inhibited by heparin, and it was retained on a heparin-Sepharose column. Its molecular weight, as assessed by Sephacryl S-200 gel filtration, ranges from 40,000-65,000. Although in many aspects EDMF is similar to vascular permeability factor-vascular endothelial growth factor, this was not detected in endothelioma cell supernatants, as assessed by enzyme-linked immunosorbent assay, thus indicating that EDMF might be related to, but is not identical with, vascular permeability factor. Our findings support the notion that recruitment of host endothelial cells by endothelioma cells in vivo might be mediated by a still unidentified, soluble factor that stimulates and directs endothelial cell migration.

Animals↗
PubMed1993

Enhancement of metastatic potential of murine and human melanoma cells by laminin receptor peptide G: attachment of cancer cells to subendothelial matrix as a pathway for hematogenous metastasis.

BACKGROUND: Stable anchorage of circulating cancer cells to the vasculature is a critical step in the formation of hematogenous metastases. Although the basement membrane glycoprotein laminin clearly plays a crucial role in this event, the exact interactive pathways among cancer cells, laminin, and the vessel wall have not been elucidated. In a previous study, we identified synthetic peptide G, which contains the laminin-binding domain of the 67-kd laminin receptor and which inhibits tumor cell adhesion to endothelial cells. PURPOSE: To assess the role of the interaction between laminin and the 67-kd laminin receptor in hematogenous metastasis formation, we studied the effect of peptide G on melanoma cell behavior in vivo and in vitro. METHODS: The effect of peptide G and control peptides was studied in vivo on lung retention and colonizing potential of murine (B16BL6) and human (A2058) melanoma cells injected intravenously in C57BL/6 and nude mice, respectively. In addition, their effect on cell adhesion and chemotaxis to laminin and on binding of iodine 125-labeled laminin to cells was studied in vitro. RESULTS: In vivo, pretreatment of cells with peptide G resulted in a two- to 10-fold significant increase in the number of experimental lung metastases. A significant relative increase in lung retention of peptide G-treated tumor cells was observed 48 hours after injection, although after 4 hours a partial reduction was observed. In vitro, peptide G significantly increased laminin binding and cancer cell adhesion to laminin and subendothelial matrix, whereas chemotaxis to laminin was significantly inhibited. CONCLUSIONS: Peptide G differentially affected the biological response of cancer cells to laminin. In vitro, it increased laminin binding and cell adhesion to laminin and subendothelial matrix, whereas it inhibited cell chemotaxis to laminin. In vivo, the overall effect of peptide G was an augmentation of lung metastasis. IMPLICATIONS: Our findings suggest that direct adhesion of tumor cells to the subendothelial matrix is a main pathway for hematogenous metastases and that tumor cell-matrix interaction may be more relevant than tumor cell-endothelial cell attachment in this process.

Amino Acid Sequence↗
PubMed1992

Thrombospondin modulates basic fibroblast growth factor activities on endothelial cells.

We previously reported that thrombospondin (TSP) induces endothelial cell (EC) adhesion, spreading and motility, suggesting that it can play a role in angiogenesis. We then studied whether TSP might modulate EC response to known angiogenic stimuli in vitro. Here we describe that TSP inhibits EC chemotactic response to basic fibroblast growth factor (bFGF). Furthermore, TSP and its 140 kD fragment reduce EC proliferative response to serum and bFGF. These data support the indicated role of TSP and its 140 kD fragment in angiogenesis and in related pathologies including tumor malignancy.

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PubMedDate not supplied

MMP inhibitors: experimental and clinical studies.

Matrix metalloproteases (MMPs) are a family of structurally related enzymes that are capable of degrading proteins of the extracellular matrix. These enzymes play a role in tissue remodelling associated with both physiological and pathogenic processes. A high expression of MMPs is associated with cancer malignancy: it is related to the tumor's ability to metastasize and to the process of angiogenesis. Treatment with MMP inhibitors alone or in combination with cytotoxic therapy is an interesting novel approach to control tumor progression. The expected mechanism of action of these compounds and the difference in side effects compared to cytotoxic drugs make the definition of endpoints and the assessment of response difficult. Furthermore, it is not yet clear whether tumor vascularization or, more specifically, MMP expression/activation should be a criterion of eligibility for this kind of treatment. This review provides an overview of the characteristics of MMPs and their role in tumor progression, metastasis and angiogenesis. Preclinical and clinical studies with synthetic MMP inhibitors are described. The presence of MMPs in biological fluids of patients and their use in prognostic evaluation and in determining the efficacy of treatment with MMP inhibitors is discussed.

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