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D M Form

Publications and source records attributed to D M Form.

4 recordsLinked to original sources

Endothelial cell proliferation during angiogenesis. In vitro modulation by basement membrane components.

Modulation of the behavior of microvascular endothelial cells during angiogenesis has been observed to correlate with changes in the extracellular matrix. These reports prompted a comparison of the growth of microvascular endothelial cells on monolayers of various matrix components in vitro. Over a 5 day period, the proliferation of these cells was significantly greater on laminin than on either plasma fibronectin, the interstitial collagen types I and III, or on the basement membrane collagen type IV. Proliferation of the microvascular endothelial cells was compared with that of bovine aortic endothelial cells and bovine aortic smooth muscle cells on the same matrices. All three cell types grew significantly more rapidly on laminin than on fibronectin. The aortic endothelial cells differed from their microvascular counterparts in that the growth of these large vessel endothelial cells on the collagenous matrices (types I and III, or type IV) was not significantly different from that observed for laminin, but was greater than the relatively slow growth seen on plasma fibronectin. Further comparison of the growth of the microvascular endothelial cells on the two basement membrane components, laminin and type IV collagen, demonstrated that the growth of these cells on laminin can be modulated by the presence of type IV collagen. This was true either if the two matrices were combined as a mixed layer, or if the laminin was specifically bound to a layer of type IV collagen, more closely simulating the distribution of these molecules in a basement membrane. Examination by immunoperoxidase of in vivo model of neovascularization in the murine cornea revealed a temporally staggered appearance of basement membrane components. The appearance of laminin was found to occur throughout the newly formed vessels, as well as in individual cells at the migrating, proliferating tips. In contrast, the appearance of type IV collagen correlated with lumen formation and was not detected at the vessel tips. The results of this study suggest that the temporally ordered synthesis of specific matrix components plays a significant role in orchestrating the growth and differentiation of endothelial cells during the highly integrated set of responses known as angiogenesis.

Animals↗

Pathogenesis of tumor desmoplasia. II. Collagens synthesized by line 1 and line 10 guinea pig carcinoma cells and by syngeneic fibroblasts in vitro.

For the investigation of the pathogenesis of desmoplasia, the capacities to synthesize collagen in vitro of 2 bile duct carcinomas (lines 1 and 10) of Sewall-Wright inbred strain 2 guinea pigs and of syngeneic dermal fibroblasts were studied. Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence. Line 1 cells also synthesized small amounts of collagenase-sensitive protein. Neither line 1 nor line 10 cells synthesized detectable collagen type I, III, or V. Only about 1% of [14C]proline incorporated by tumor cells was found in collagenase-sensitive protein. In contrast, dermal fibroblasts synthesized 4 and 128 times as much collagenase-sensitive protein as line 10 and line 1 cells, respectively, amounting to 20% of total protein synthesized. Fibroblasts produced mostly collagen types I and III, in a ratio of 7:1, and smaller amounts of collagen type V. Thus lines 1 and 10 carcinoma cells produce primarily basement membrane collagen, whereas interstitial collagens, abundant in desmoplastic tumor stroma, are fibroblast products.

Animals↗

Pathogenesis of desmoplasia. I. Immunofluorescence identification and localization of some structural proteins of line 1 and line 10 guinea pig tumors and of healing wounds.

The structural proteins of the scirrhous line 1 and the medullary line 10 bile duct carcinomas, both syngeneic in strain 2 Sewall-Wright inbred guinea pigs, were studied. Tumor structural proteins were compared with those of healing wounds. A provisional stromal matrix of cross-linked fibrin and fibronectin was initially deposited in both tumors and wounds and was subsequently replaced by granulation tissue containing collagen types I and III. The amounts of stromal fibrin-fibronectin and collagen were characteristic of each tumor: Line 1 contained significantly greater amounts than line 10. These differences were augmented when line 1 tumor rejection was prevented with cyclosporine, permitting time for stromal maturation. In tumors and wounds laminin and collagen type IV were found only in basement membranes. The findings suggest that 1) tumor desmoplasia is analogous to wound healing, 2) both processes involve replacement of an antecedent fibrin-fibronectin provisional matrix, 3) the extent of fibrin-fibronectin is characteristic of each tumor, and 4) tumor desmoplasia correlates with the amount of fibrin-fibronectin matrix deposited.

Animals↗

PGE2 and angiogenesis.

The angiogenic capability of PGE2 was tested by implanting pellets of an ethylene vinyl acetate slow release polymer containing PGE2 on the chorioallantoic membrane of 8-day-old chicken embryos. Elvax pellets releasing approximately 0.2, 2.0, or 20 ng/day PGE2 were found to induce neovascular responses. In contrast, pellets releasing 2.0 or 20 ng/day of either PGA2, PGF2, or TXB2 did not appear to be angiogenic when compared with PGE2. These release rates of PGE2 are similar to those reported for a variety of tumors, activated macrophages, inflammatory exudates, and rheumatoid synovia, suggesting that PGE2 may be a key factor in various neovascular reactions.

Allantoin↗