醣化酵素在老鼠胰臟癌細胞轉移至肝臟的角色

Angiogenesis is essential for the growth of primary tumor and, as shown in our previous
studies , is also the only significant intravasation-related metastatic factor. Tumor’ll secrete
or induce many angiogenic factors to induce neovascularizatioin. Endothelial cells stimulated by
these angiogenic factors such as vascular endothelial growth factor, secrete matrix
metalloproteinase-2 (Gelatinase A) which contributes to degradation of basement membrane in
microvessel walls. This breakdown in the vascular basement membrane may facilitate the
extravasation of endothelial cells during formation of neovascularization sprouts, as well as
intravasation of tumor cells into lumen. If tumor vessel formation is rapid and haphazard and
endothelial proliferation is insufficient or endothelial junctions are unstable, cancer cells may be
exposed to the lumen and passively enter the circulation during the angiogenic process. Thus,
in contrast to the present view “metastasis marks the end in a sequence of genomic changes
underlying the progression of an epithelial cell to a lethal cancer”, these results imply that tumor
cells may passively enter the circulation early during multistep tumorigenesis.
From the synoptic analysis of cytogenetic data from thousands of solid tumors, it was deduced
that the number of cytogenetic imbalances per tumor reflects to some extent the biological age of
the tumor. Hence, the relative small number of chromosomal aberrations in many latent
disseminated cells suggests they left the primary site early and the further accumulation of
imbalances may have been decelerated, perhaps by environmental constraints, which leads to the
tumor dormancy.
Results of our studies, tumor dormancy, and cancer of unknown primary
syndromes all stress the importance of soil to develop established metastatic growth. Thus,
we’re going to focus further studies on metastatic steps after extravasation.
As previous described, tumor depends on angiogenesis to sustained growth. Once the tumor
mass reaches a diameter of ~2 mm, establishment of new vascular system is essential for its
survival. Until then, endurance in hypoxic condition is essential for its survival. In liver, there is a
plenty storage of glycogen and these glycogen can be used as substrate of glycolysis in an anoxic
condition. Theoretically, tumor cells with enzymes for glycolysis (such as enolase α) may have a
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greater chance to survive in liver and remained in dormant state. To test this hypothesis, we’ll try
to increase the liver metastasis by injecting murine-enolase-overexpressing pancreatic cancer
cells.