Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor.

Kerbel, Robert S.; Lagarde, Alain E.; Dennis, James W.; Donaghue, T. P.

doi:10.1128/mcb.3.4.523

Cited by 122 publications

(82 citation statements)

References 60 publications

(77 reference statements)

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“…The mechanism responsible for in vivo neoplastic transformation of the host cells by the injected tumour cells is not known. Formation of somatic cell hybrids between the injected tumour cells and the murine host cells, followed by complete elimination of human chromosomes, has been proposed as a possible mechanism for such a transformation (Weiner et al, 1972;Kerbel et al, 1983;Kerschmann et al, 1995). We rule out this possibility in the present study because FISH analysis with a total human DNA probe did not show a signal in either metaphase or interphase cells of the resulting murine cells.…”

Section: Discussionmentioning

confidence: 71%

Can cancer cells transform normal host cells into malignant cells?

Pathak

Nemeth²,

Multani³

et al. 1997

Br J Cancer

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Summary A human prostate tumour cell line, LNCaP C4-2, when injected into athymic male nude mice, produced tumours containing:(1) only human cancer cells similar to those injected; (2) only murine stromal cells containing abnormal chromosome constitutions; or (3) both human prostate cancer cells similar to those injected and the transformed murine stromal cells with altered chromosome constitutions.Karyotypic analysis of murine metaphases from all the host-derived tumours showed mostly pseudodiploid chromosome constitutions, with multiple copies (amplification) of mouse chromosome 15 and the absence of a typical Y chromosome. Fluorescence in situ hybridization analysis of these murine cells, using a biotin-labelled total human DNA painting probe, further demonstrated the absence of human DNA and the presence of only mouse metaphase and interphase cells in these transformed stromal cells. These results suggest that cancer cells are capable of inducing neoplastic transformation in stromal cells of the host organ by some, as yet unknown, epigenetic mechanism(s).Keywords: malignant transformation; tumour-stroma interaction; fluorescence in situ hybridization; pseudodiploid karyotype; prostate cancer progression; epigenetic mechanism of carcinogenesis Although the athymic mouse and rat are not natural hosts for the study of the in vivo biology of human neoplasms, they provide excellent models for the growth and maintenance of human tumours in vivo (Fidler, 1986) and for the study of reciprocal cellular interaction between tumour cells and host stroma (Wu et al, 1994). For many tumour biology experiments, the nude mouse routinely serves as a 'biological incubator' for primary and established tumour cells for selecting derivative cell lines with differing metastatic properties and for therapeutic trials monitoring tumour growth and levels of tumour or serum biomarkers (Fidler, 1986(Fidler, , 1990. The focus of the present communication is to document the tumour-stroma interaction that resulted in the induction of host stromal cells to assume non-random genetic alterations.When human tumour cells are injected into nude murine animals, quite frequently human tumour cells grow, but other possibilities also exist (Treit et al, 1980;Goldenberg and Pavia, 1981;Bowen et al, 1983;Hsu and Pathak, 1989;Gupta et al, 1990). In earlier experiments in which we injected human breast cancer cells into the nude mouse, the tumours produced in the host consisted of mouse cells with abnormal metaphases containing double-minute chromosomes (Bowen et al, 1983). Three types of tumour cells were harvested from such an experimental tumour model: (1) The purpose of this study was to investigate whether there were specific cytogenetic abnormalities present in several murine stromal tumours that developed after the injection of human C4-2 tumour cells that metastasized as bony tumour deposits (Thalmann et al, 1994;Wu et al, 1994). We report here cytogenetic findings from the resulting host stromal tumour cell lines from six athymic mice bearing...

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Section: Discussionmentioning

confidence: 71%

Can cancer cells transform normal host cells into malignant cells?

Pathak

Nemeth²,

Multani³

et al. 1997

Br J Cancer

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“…Exchange of membrane microparticles may also be a part of this process (18,21,25). Finally, cell fusion (thought to be common in cancer cells) may lead to sharing of proteins between adjacent cells (22,23). Our data seem to agree best with a contact mediated transfer, based on the absence of transfer in the filtered medium experiments, unaltered size of AqMDR cells, and instability of the transferred protein in the sorted cells; the results argue against microparticle or fusion-mediated transfer.…”

Section: Discussionmentioning

confidence: 99%

Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells

Levchenko

Mehta

Niu

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

171

156

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The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in many tumor types. Here, we report intercellular transfer of functional P-gp from P-gp-positive to P-gp-negative cells in vitro and in vivo. The expression of acquired P-gp is transient in isolated cells but persists in the presence of P-gppositive cells or under the selective pressure of colchicine. The intercellular transfer of functional P-gp occurs between different tumor cell types and results in increased drug resistance both in vitro and in vivo. Most importantly, the acquired resistance permits tumor cells to survive potentially toxic drug concentrations long enough to develop intrinsic P-gp-mediated resistance. P-gp transfer also occurs to putative components of tumor stroma, such as fibroblasts, raising the possibility that multidrug resistance could be conferred by resistant tumor cells to critical stromal elements within the tumor mass. This is the first report, to our knowledge, that a protein transferred between cells retains its function and confers a complex biologic property upon the recipient cell. These findings have important implications for proteomic analyses in tumor samples and resistance to cancer therapy.cell-cell communication ͉ multidrug resistance phenotype C ell-cell communication is an inherent feature of all life forms from bacteria to humans. A frequent result of cell-cell communication is collective population behavior that can potentially lead to complex phenotypes not observed in separate individual cells, e.g., in development or tumor formation (see, for example, ref.

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“…Spontaneous fusion in vivo between unidentified host cells and tumor cells and its possible contribution to tumor progression and metastasis were suggested some time ago based on the experiments with the MDW4 tumor in DBA/2 mice. 26,27 It would be of interest to study whether some human carcinomas could attract stem cells by mimicking a stem cell "niche" microenvironment thus directly engaging normal stem cells into malignant process. Neural stem cells might be present in many (if not all) peripheral tissues and therefore may represent likely and readily accessible cellular targets for direct engagement into malignant process via cell fusion.…”

Section: Stem Cell Cancer Hypothesismentioning

confidence: 99%