Malignant Tumor Cell Lines Research Articles

血小板中に存在するしゅよう細胞増殖因子について

Three growth factors (acidic, neutral and basic) were partially purified from platelet lysate by DE 52 cellulose chromatography. The basic factor was proved to be identical to PDGF hitherto reported. The growth promoting activity of these three factors for variouse cell lines was studied in vitro.Basic factor (PDGF) promoted growth of fibroblast (Swiss 3T3, SV 3T3) as has been described previouly, but had relatively less activity of growth promotion to malignant tumor cell lines (K562, HeLa and RPMI 4788).On contrast, acidic factor strongly stimulated the proliferation of tumor cells and, to less extent, of fibroblasts.Malignant cells (K562) were synchronized to pre S phase by addition of excess of thymidine and hydroxyurea, and thus synchronized cells were also proved to be more sensitive to acidic factor than to PDGF, indicating that the sensitivity is not related to cell cycle.

Selective killing of human malignant cell lines deficient in methylthioadenosine phosphorylase, a purine metabolic enzyme.

Seven out of 31 (23%) human malignant tumor cell lines had no detectable methylthioadenosine phosphorylase activity (less than 0.001 nmol/min per mg of protein), assayed with 5'-chloroadenosine as substrate. The enzyme-deficient cell lines were derived from five leukemias, one melanoma, and one breast cancer. None of 16 cell lines of nonmalignant origin, derived from lymphocytes, fibroblasts, and epithelial cells, lacked the enzyme (range, 0.156-1.447 nmol/min per mg of protein). As detected by autoradiography, intact enzyme-positive cell lines normal immature bone marrow cells, and four specimens of malignant tumor cells incorporated the adenine moiety of 5'-chloroadenosine into nucleic acids; however, no enzyme-deficient cell lines used 5'-chloroadenosine. When both types of cell lines were cultured in a medium containing 0.4 microM methotrexate, 16 microM uridine, and 16 microM thymidine (or 10 microM azaserine alone), no cells grew. If methylthioadenosine was added to the same medium, only enzyme-positive cells increased in number; most enzyme-deficient cells were dead after 3 days. Thus, human malignant tumor cell lines naturally deficient in methylthioadenosine phosphorylase could be selectively killed when de novo purine synthesis was inhibited and methylthioadenosine was the only exogenous source of purines.

In vitro and in vivo selection of two Lewis lung carcinoma cell lines.

Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.