A poorly differentiated
medullary carcinoma of human stomach, designated
HY-1, was successfully transplanted to nude mice by either the subcutaneous or intramuscular route for five generations. The transplanted
tumor showed spontaneous lung
metastases in nearly 100% of KSN and Balb/c female nude mice. There were over 20 visible lung metastatic nodules in KSN and Balb/c nude mice bearing
tumors for over 80 days. Immunostaining of
type IV collagen and electron microscopy revealed that
tumor cells were often in direct contact with basement membrane (BM) of
tumor blood vessels in the primary
tumor tissue. At the site of contact between
tumor cells and vascular BM, focal disappearance of the BM, disruption of endothelial cells and entry of
tumor cell clusters into vascular lumen were observed. Immunostaining of
72 kDa gelatinase/type IV
collagenase demonstrated that
tumor cells expressed this
enzyme in their cytoplasm. These results suggest that spontaneous
metastasis of this
tumor may be partly due to a marked tendency to vascular invasion involving the following sequential events:
tumor cell contact with vascular BM, BM degradation possibly by 72 kDa
gelatinases and endothelial disruption. This model could be a useful tool for understanding the mechanism of hematogenous
metastasis of human
gastric cancer.