Human villous adenomas engrafted into scid mice survive for prolonged period without malignant transformation.

Abstract

Human villous adenomas are thought to represent premalignancies that subsequently give rise to colorectal adenocarcinomas. Currently there is no in vivo model in which to study the dedifferentiation and malignant transformation of these tumors. We establish here that human villous adenomas can be successfully engrafted into severe combined immunodeficient (scid) mice. Furthermore, these xenografts remain viable for up to 18 mo after either a subcutaneous or intraperitoneal inoculation of the human tissue. Tumors grew slowly and secreted a clear mucinous fluid. Examination of the tumors histologically at 1, 4, and 12 mo after implantation revealed that the villous polypoid structure was maintained and islands of atypical cells were observed within pockets of mucin surrounding the adenomatous tissue. No gross or histologic evidence of malignancy was detected throughout the 20-mo observation period. The human identity of the cells in the graft was confirmed by DNA in situ hybridization with a human-specific probe. We conclude that the human-scid xenograft described here represents a viable animal model with which to study the potential malignant dedifferentiation of villous adenomas over a prolonged period of time and to evaluate the possible contribution of selected oncogenic vectors on the malignant transformation of these adenomas. (J. Clin. Invest. 1994Invest. . 94:2153Invest. -2157

Peyronie's disease fibroblasts demonstrate tumorigenicity in the severe combined immunodeficient (SCID) mouse model

“…It has served as a well-recognized animal model for malignant disease and hematological disorders but more recently has been used in the study of benign diseases. [20][21][22][23]25 Awwad et al 22 in an attempt to develop an animal model for endometriosis, studied the results of blind intra-peritoneal injection of endometrial tissue into SCID mice. They found a 96% successful implantation rate and conservation of normal morphologic features on staining of the tissue.…”

“…These properties have allowed the development of animal models for research in many areas where it was not previously possible, including solid and hematologic malignancies. 20,21 SCID mice have also been used in the exploration of benign diseases. 22,23 Cells that demonstrate tumorigenic potential are by definition biologically transformed.…”

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer

“…Human colorectal tumors once implanted will propagate and metastasize in the severe combined immunodeficient (SCID) mouse. 1,2 Furthermore, these tumors maintain their human genetic make up through multiple repassages. This model has proven to be a useful tool to evaluate human cancers, such as colorectal, for their growth patterns, cell surface receptors, and the therapeutic effects of antitumoral agents.…”

Transplantation of a human ovarian cystadenocarcinoma into severe combined immunodeficient (SCID) mice — formation of metastases without significant alteration of the tumour cell phenotype

“…A similar observation on a parallel growth behaviour study of human cells in patients and in SCID mice has been made using colorectal villous adenomas. Human colorectal villous adenoma engrafted for a prolonged period into SCID mice did not show any malignant transformation and hence behaved as it would in a patient (Bumpers et al 1994). It is of particular interest that cells grown in suspension were able spontaneously to form solid tumours again when engrafted in the ovary or when Ovarian carcinoma in SCID mice 225 injected subcutaneously when the SoTü cells formed cysts as in the primary tumour.…”