Cell fusion in tumor development and progression: Occurrence of cell fusion in primary methylcholanthrene‐induced tumorigenesis

Abstract

Definitive evidence for the occurrence of cell fusion in tumorigenesis was sought in methylcholanthrene-induced sarcomas. This was approached by using allophenic mice generated from strains differing for electrophoretic variants of the ubiquitous, dimeric enzyme glucose phosphate isomerase, with fusion assessed by heterodimer formation. Eight-three carefully trimmed primary tumor samples (from 23 individual tumors in allophenic mice) were analyzed, as were 1,140 clones derived from them. In all primary tumor samples, zymograms exhibited one GPI homopolymeric band. Expression of a hybrid band (indicative of a fusion event) was not observed in these samples. However, 9 (0.8%) of the tumor clones demonstrated a distinct and reproducible hybrid band which was uniformly lost upon recloning. Our data suggest that cell fusion, although uncommon, occurs in the clonogenic cell fraction during primary MCA tumorigenesis and is followed rapidly by chromosome segregation.

Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants

“…In cancer research, cell fusion has been speculated to play important roles in several aspects of tumor progression, including generation of cancer stem cells (8), acquisition of metastasis ability (7), and multidrug resistance (11). Cancer cells can have considerably high rate (up to 1%) of fusion in vivo in experimental tumor models (10). Recent findings that chronic inflammation dramatically increases the frequency of cell fusion between hematopoietic cells with various cell lineages (24, 25) may help explain the high fusogenicity of tumor cells, as inflammation is often associated with the tumor microenvironment (26).…”

“…An alternative theory of metastasis progression has also been proposed that argues for rapid acquisition of metastatic phenotypes through fusion between tumor cells or between tumor cells and certain normal cells, such as macrophages (6)(7)(8)(9), rather than requiring the progressive accumulation of independent genetic or epigenetic alterations in a single cell lineage. Given that a 1-cm 3 tumor of Ϸ10 9 cells is estimated to harbor as many as 10 5 proliferating hybrid cells produced by spontaneous cell fusion (6,10), the contribution of cell fusion to the phenotypic evolution of tumors cannot be overlooked.…”

Cell fusion promotes chemoresistance in metastatic colon carcinoma

“…[7][8][9] Cell fusion is a process in which two cells become one by merging their plasma membranes. [10][11][12] The role of cell fusion in metastasis has been recently demonstrated. This represents an efficient means of rapid phenotypic evolution during tumor progression that make cells with new properties at a rate exceeding that achievable by random mutagenesis.…”

Heterogeneity of MHC-class-I antigens in clones of methylcholanthrene-induced tumors. Implications for local growth and metastasis

“…The behavior of such chemically induced tumors in syngeneic animals has been extensively studied (Old et al, 1962;Klein et al, 1960;Fortuna et al, 1990). However, few studies have compared the biological behavior, immune response and presence or absence of MHC class-I antigens at the clonal level (Schirrmacher et al, 1981;Ogata et al, 1986; PCrez er al., 1989).…”