Adhesion of cancer cells to endothelium is considered an essential step in metastasis. However, we have shown in a previous study that when rat colon cancer cells are administered to the vena portae, they get stuck mechanically in liver sinusoids. Then, endothelial cells retract rapidly and cancer cells bind to hepatocytes. We investigated the molecular nature of these interactions between colon cancer cells and hepatocytes. Cancer cells in coculture with hepatocytes became rapidly activated with distinct morphological changes. Cancer cells formed long cytoplasmic protrusions towards hepatocytes in their close vicinity and these protrusions attached to microvilli of hepatocytes. Then, adhering membrane areas were formed by both cell types. Integrin subunits αv, α6 and β1 but not αL, β2, β3 and CD44 and CD44v6 were expressed on the cancer cells. In conclusion, colon cancer cells show an active behaviour to bind to hepatocytes, likely involving the integrin subunits av, a6 and B1, indicating that early events in colon cancer metastasis in liver are distinctly different than assumed thus far.
Testosterone (T), dihydrotestosterone (DHT), androstenedione (\g=D\4) and dehydroepiandrosterone (DHA) were measured by radioimmunoassay in peripheral plasma, uterine vein plasma, ovary and placentae within the last 3\p=n-\4days of pregnancy in Sprague-Dawley rats. In the uterine vein, T and \ g=D\ 4 levels were significantly higher than those reported in the peripheral plasma at any particular day of late pregnancy. In peripheral plasma as in uterine vein plasma \ g=D\ 4 and T gradually decreased from day 20 to term (\m=-\63% for \ g=D\ 4 and approximately \m=-\45%for T) whereas DHT concentrations were unchanged. This decline is concomitant with a similar pattern of change in the placentae; indeed placental concentrations of \ g=D\ 4 and T decreased significantly from day 19 to 22 (\m=-\63 and \m=-\79%,respectively) and were positively correlated with the levels of both androgens in uterine venous and peripheral plasma. Thus it was concluded that in the late phase of pregnancy in the rat circulating \ g=D\ 4 and T originate from placentae. In contrast, ovarian androgen concentrations showed a sharp increase from day 21 to term: 58% for DHA, 49% for \ g=D\ 4, 87% for T and 24% for DHT. It is suggested that these increasing concentrations of ovarian androgens could be related to the next ovulatory cycle.In the mid-pregnant rat, recent studies have as¬ signed increasing importance of androgens for maintenance of pregnancy: testosterone (T) is an
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