Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype

Abstract

The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i) after transplantation into the undisturbed subcutaneous connective tissue of rats, and (ii) after transplantation into experimentally induced subcutaneous granulation tissue in rats. For the latter experimental situation, a subcutaneous "tissue chamber" was designed allowing fragments of tumor tissue to be transplanted into the very center of developing granulation tissue. In the undisturbed subcutaneous tissue, the whole tumor was generally encapsulated, and the tumor cells were arranged in compact groups with a strong tendency to form acini. In the pre-formed granulation tissue, on the other hand, the tumor tissue closely matched descriptions of invasive colon carcinomas in the literature and met the criteria for the "invasive morphotype". In this situation, the tumor consisted of thin, unorganized, widely dispersed strands of irregular tumor cells with numerous protrusions that deeply penetrated the surrounding matrix. Our results show that an invasive morphotype can be evoked by pre-inducing granulation tissue at the transplantation site.

Role of tissue stroma in cancer cell invasion

“…Alteration of the stromal host compartment is due to an imbalance in the cytokine profile, resulting from the oncogenic changes in the cancer cells. Experimental animal models have demonstrated that cancer invasion is stimulated by the wound-healing stroma [9]. This observation suggests that growth factors implicated in wound healing such as transforming growth factor-β1 (TGF-β1 = TGF-β) [29] and platelet-derived growth factor (PDGF) [30] may also play a role in changing the stromal host compartment in cancer.…”

“…Cancer invasion is stimulated by wounding of the host tissue as demonstrated by rat colon adenocarcinoma cells that were transplanted into experimentally induced subcutaneous granulation tissue and in undisturbed subcutaneous tissue. In the pre-formed granulation tissue the tumours closely resembled invasive colon carcinomas, whereas in the undisturbed subcutaneous tissue the tumour was encapsulated and non-invasive [9]. Local factors act also at the site of metastasis.…”

Modulation of the plasminogen activation system by inflammatory cytokines in human colon carcinoma cells

“…Tumour-associated macrophages recruited by the inflammatory reaction associated with cancer diseases have been suggested to favour or, alternatively, to interfere with the invasive growth of cancer cells (Mantovani et al, 1992;Dingemans et al, 1993;Levine and Saltzman, 1990; Van der Boschet et al, 1992;Orosz et al, 1993;Quin et al, 1993). These conflicting observations are possibly related to the pleiotropic biological effects mediated by cytokines produced by the host in response to tumour invasion and metastasis.…”

Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver

“…As for the mechanism of local recurrence, it should be noted that hepatic recurrence, in rats treated with laser or resection, was always located within or close to granulation tissue. Tissue trauma and healing enhances the take and growth of both circulating and implanted tumour cells, which may be due to local growth factors, angiogenesis and/or clot formation (van den Brenk et al, 1973;Withers and Milas, 1973;Eggermont et al, 1987;Orr and Warner, 1987;Weiss et al, 1988;Murthy et al, 1989;Loizidou et al, 1991;Dingemans et al, 1993). There is a two-to threefold rise in transaminases shortly after laser treatment (Bosman et al, 1991;Masters et al, 1992;van Hillegersberg et al, 1994).…”

“…These unwanted effects of surgery may be caused, at least partly, by immunosuppression and by the release of growth factors involved in tissue healing (Eggermont et al, 1987;Loizidou et al, 1991;Panis et al, 1992;Pollock et al, 1992;Dingemans et al, 1993;Oka et al, 1994;Slooter et al, 1995). One of the advantages of local tissue destruction is that the trauma is small compared with surgery.…”