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KMID : 0371319950490050700
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Journal of the Korean Surgical Society
1995 Volume.49 No. 5 p.700 ~ p.707
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Resistance of Highly Metastatic Variants of Human Pancreatic Cancer Cells to the Growth Inhibitory Effect of Transforming Growth Factor-b1(TGF-b1)
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Abstract
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The purpose of the present study was to examine the sensitivity of a slow-growing(SG) poorly metastatic and fast-growing(FG) highly metastatic human pancreatic cancer cells to TGF-β1, a potent mitogenic inhibitor of epithelial cell growth; a
TGF-β1
refractory phenotype may be relevant to their metastatic potential. The poorly metastatic SG incubated with TGF-β1 refractory phenotype may be relevant to their metastatic potential. The poorly metastatic SG incubated with TGF-β1(10 ng/ml) for
48
hr
showed altered cellular morphology while the highly metastatic FG and L3. 4 did not show morphological changes. The growth of SG measured by[3H]-TdR incorporation was in hibited by 50% when incubated with TGF-β1(5 ng/ml) under low serum
concentrations(0.5%). TGF-β1 mediated growth inhibition of SG was dose dose dependent(0.25~5ng/ml). On the other hand, neither FG nor L3.4 showed significant growth inhibition. However, SG suppression was not asseciated with TGF-β1-induced
apoptosis.
In addition, FG and L3.4 produced higher levels of endogenous TGFβ1(113.28±20.73 pg/ml, and 160.13±2.20 pg/ml, respectively) compared to SG(12.75±1.22 pg/ml) as measured from culture surpernatant. These findings suggest that highly metastatic
variants of human panreatic cancer cells(FG and L3.4) have escaped the negative growth regulation of TGF-β1. High levels of TGF-β1 secretion by FG and L3.4 may favor their preferential growth by suppressing the growth of competing normal cells
in
their microenvironment.
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KEYWORD
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