The Structure of Tumours Derived from Mouse Cells after “Spontaneous” Transformation in vitro

Abstract

SUMMARY.-The histological structure of 58 primary tumours derived from spontaneously transformed tissue culture cell lines from embryonic (14-16 days), young (3-20 days) and old (28-34 months) C3H and C57 mice is described. Although the cell lines were derived from a number of different organs the tumours were similar in morphology. The pattern was mixed, with " fibrosarcomatous ", " myxoid ", " epithelioid " and giant cell areas. The tumours resemble some types of haemangiopericytoma.ALTHOUGH spontaneous neoplastic transformation in vitro has been studied by many workers there have been relatively few detailed studies on the nature of the tumours developing after implantation of transformed cells into syngeneic mice. In most cases these have been classified as " fibrosarcomas " (see e.g. Nettleship et al., 1943;Evans et al., 1964;Cornell, 1969). The purpose of this paper is to describe the morphology of such tumours which arose from cell lines established from a number of different organs from young and old C57 and C3H mice. The establishment of the cell lines and the ultrastructural morphology of the tissue culture cells have been described in earlier papers (Franks and Henzell, 1970;Franks and Wilson, 1970). The histochemistry, enzyme biochemistry and ultrastructure of the tumours will be described in a later paper. MATERIAL AND METHODSNineteen tumour-producing cell lines were established from embryo (13-18 days), young (3-20 days) and old (28-34 months) C3H and C57BL at Icrf mice. Details of the tissue culture methods used for the young and old mice are described in an earlier paper (Franks and Henzell, 1970). The embryo lines were established by Dr. S. Lan from whole embryos, using methods described by Todaro and Green (1963). The other lines were derived from the following organs-kidney, bladder, lung, tongue, heart, prostate, brain, spinal cord and nerve. The tissue culture cells were removed from their containers by the method by which they were usually transferred, i.e. trypsinisation or scraping, and centrifuged. The pellet was resuspended in about 0-6 ml. of tissue culture medium. Routinely 0-2 ml. of the suspension was injected subcutaneously into syngeneic hosts 3-6 months old. Approximately 3 x 106 cells were inoculated into each mouse. Two of the tumours were implanted intraperitoneally and two intraocularly, using the method of Grobstein (1950). In all 17 primary tumours were established from different

Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

“…Despite the challenges in demonstrating unequivocal efficacy, there is little controversy that intravenous administration of MSCs (mostly marrow derived, but also adipose) is clinically safe, with post infusion febrile reaction being the sole adverse event likely associated with their use(Lalu et al, 2012). Whilst murine culture adapted MSCs are prone to spontaneous immortalization and latter transformation – a feature observed nearly 50 years ago(Franks et al, 1970), claims of similar genetic instability and tumorigenicity for human culture expanded MSCs have been debunked(Sensebe et al, 2012).…”

The ability of normal mouse cells to reduce the malignant potential of transformed mouse bladder epithelial cells depends on their somatic origin

“…With the exception of HEB 11 and HEB 13, all the hybrids produced tumours which were typical leiomyosarcomas ( Fig. Sa-d) with some fibrosarcomatous areas and myxoid areas identical in structure with those produced by in vitro-transformed mesenchymal cells (see Franks et al 1970). In the smaller tumours there was some peripheral inflammatory response around the invading edge with occasional plasma and round cells, although the reaction was mainly of polymorphs.…”

The structure of tumours derived from mouse submandibular gland epithelium transformed in vitro

“…One cell line produced tumours with both epithelial and leiosarcomatous components (Fig. 8) the latter being similar in structure to the tumours produced by spontaneously transformed mesenchymal cell lines (Franks, Chesterman and Rowlatt, 1970). Although all tumours had invaded the surrounding muscle and vascular invasion was common, metastases were not found.…”

“…In any work on epithelial carcinogenesis in vitro, it is important to establish the epithelial nature of the tumours produced, particularly as many mesenchymal tumours from in vitro-transformed cells may have an anaplastic epithelial-like pattern (Franks et al, 1970). The structure of the tumours we have described shows beyond question that the cells which had been transformed in vitro were epithelial.…”