PubMed · 2922383
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
E Jimenez, M Vogel. 1989. [Comment on a previous article].. https://pubmed.ncbi.nlm.nih.gov/2922383/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The human epidermoid carcinoma cell line HEp-3 gives rise to spontaneous metastases in nude mice and in the chick chorioallantoic membrane (CAM) assay system. Cells passaged continuously on the CAM retain their ability to form metastases, while cells carried in vitro lose metastatic potential with time. A HEp-3 cell line derived from a highly metastatic CAM tumor was grown continuously in vitro for 16 weeks. At 2-week intervals the cells were tested on the CAM for metastatic ability and assayed for expression of urokinase-type plasminogen activator (uPA) and the M(r) 92,000 and M(r) 72,000 gelatinase/type IV collagenases, enzymes the expression of which has previously been shown to correlate with tumor cell dissemination. Expression of proteins which modulate the degradative potential of these enzymes, plasminogen activator inhibitors 1 and 2 (PAI-1, PAI-2), uPA receptor, and tissue inhibitors of metalloproteases 1 and 2 (TIMP-1 and TIMP-2), were also assayed. As previously reported the metastatic ability of these cells decreased with time in culture and was almost completely lost by 8 weeks in vitro. Secreted uPA activity remained essentially unchanged, even though uPA mRNA levels decreased with time. There was also a decrease in PAI-1 and PAI-2 mRNA. However, PAI-1 protein concentration in conditioned medium remained relatively constant, and only trace amounts of PAI-2 protein could be detected in cell lysates. Steady-state levels of uPA receptor were lowest at 2 weeks then increased sharply at 4 weeks and remained relatively constant thereafter. A decrease in secreted M(r) 92,000 and M(r) 72,000 gelatinase activities and their corresponding mRNAs was observed well after the loss of the metastatic phenotype. During the 16 weeks in culture TIMP-1 mRNA levels changed slightly, while TIMP-2 mRNA increased more than 2-fold. These data suggest that a metalloproteinase other than the gelatinase/type IV collagenases may be involved in HEp-3 metastasis.
In this study, we have determined the ability of suramin to inhibit angiogenesis in the chick chorioallantoic membrane. Suramin alone showed significant angiostatic activity in a dose-related manner. Suramin also potentiated the activity of the angiostatic steroids, cortisol-21-phosphate, 17 alpha-hydroxyprogesterone, tetrahydrocortisol, and tetrahydrocortexolone. The presence of heparin decreased the angiostatic activity of suramin. These results suggest that suramin may decrease tumor growth by inhibiting angiogenesis. These novel findings indicate that suramin, perhaps in combination with angiostatic steroids, may be the basis for important new therapeutic approaches for diseases of neovascularization.
Fertile eggs from the domestic fowl were incubated under normobaric normoxic (21% O2), hypoxic (14% O2), and hyperoxic (40% O2) conditions in order to examine the influence of the prevailing oxygen level on the growth and maturation of the chorioallantoic membrane. Eggs were sampled at regular stages throughout incubation for morphometric analysis. Under normoxic conditions, maturation of the capillary plexus occurred in two distinct stages, both of which contributed to a reduction in the thickness of the air-blood barrier. Between days 6 and 10, the capillaries sprouted and fused to form a dense plexus. Subsequently, between days 10 and 14, this plexus invaginated into the chorionic epithelium. Differentiation of the chorioallantoic membrane appeared maximal by the end of this period. Hypoxia resulted in diminished growth of the embryo and chorioallantoic membrane, but in accelerated maturation of the capillary plexus. Hyperoxia had a less marked effect but appeared to retard the final invagination of the plexus, resulting in a thicker air-blood barrier.