Multinucleation in response to cytochalasin B: a common feature in several human tumor cell lines.

Human tumor cell lines derived from melanoma, glioblastoma, and carcinoma of the prostate, bladder, and kidney multinucleated in response to growth in cytochalasin B-supplemented medium, whereas cell lines derived from normal prostate, kidney, skin, lung, and other nonmalignant diseases remained predominantly binucleate under comparable conditions. The multinucleate cytochalasin B phenotype was dissociable from the anchorage-independent phenotype of tumor cells, suggesting that these markers of cellular transformation are under separate control. These results suggest that uncontrolled nuclear division by tumor cells may be a general marker of abnormal growth or regulation.

Multinucleation in the presence of cytochalasin B by RNA tumor virus-transformed cells.

RNA tumor virus-transformed cell cultures derived from rat, mouse, hamster, and mink were examined for their response to cytochalasin B (CB), and the expression of this marker was correlated with growth in soft agar and tumorigenicity in vivo. Continuous cell lines transformed and chronically infected with Moloney murine sarcoma-leukemia virus (M-MSV-MuLV) or Kirsten murine sarcoma-leukemia virus were extensively multinucleated when treated with CB. Similarly, nonproducer Moloney murine sarcoma virus- or Rous sarcoma virus-transformed cells multinucleated in response to CB treatment, whereas uninfected or murine leukemia virus-infected cells remained predominately binucleate under comparable conditions. Rat kidney or embryo cell cultures, one to two passages after infection with M-MSV-MuLV, were highly multinucleated following CB treatment and acquired the ability to grow in soft agar. Mouse 3T3 cell lines, newly infected with M-MSV-MuLV, exhibited a moderate degree of CB-induced multinucleation. CB-induced multinucleation was directly correlated with anchorage-independent growth for most of the cell lines tested. An exception was the Moloney murine sarcoma virus-transformed mink cells which multinucleated in response to CB treatment but were unable to proliferate in soft agar. CB-induced multinucleation was directly correlated with the tumorigenicity of M-MSV-MuLV-transformed rat cells in syngeneic animals. These results demonstrate that CB-induced multinucleation is a useful in vitro growth-related marker of cell transformation by RNA tumor viruses and, in addition, show that this parameter of cell transformation is closely correlated with anchorage-independent growth in vitro and tumorigenicity in vivo.

Cytochalasin B-induced multinucleation of human tumor and normal cell cultures.

Twelve human cell cultures derived from tumors, normal tissues, and derivative cultures transformed by either a RNA tumor virus or chemical carcinogen were examined for their response to cytochalasin B (CB) and the expression of this marker was correlated with growth in soft agar and saturation density in monolayer culture. Cell lines derived from carcinoma of the bladder (T24 and RT4), kidney (Caki-1), prostate (DU 145), and breast (MCF-7) multinucleated when growth in CB-supplemented medium, whereas cell cultures derived from benign bladder epithelium (HCV-29), and normal kidney (Flow 4000) and skin (GM10) remained binucleate under comparable conditions. Human osteosarcoma (HOS) cells transformed by murine sarcoma virus (MSV) or a chemical carcinogen extensively multinucleated in response to CB treatment, relative to a morphological revertant of MSV-transformed HOS and parental HOS cells. CB-induced multinucleation was consistently correlated with the ability of cells to form colonies in soft agar but inconsistently correlated with growth to high saturation densities. These results demonstrate a differential response to CB by normal and transformed human cells and that CB-induced multinucleation provides a convenient and useful in vitro marker for neoplastic transformation.