The development of neoplasia was studied by the combined methods of cytopathology, tissue culture, and transplantation technic in chemically induced lesions of mouse uterine cervix.

The intravaginal application of benzpyrene-induced cervical dysplasia, carcinoma in situ, and invasive carcinoma. Epithelial cells from these lesions exhibited an immediate capability to establish “transformed” tissue culture cell lines. Criteria of this transformation are discussed. However, thus far none of these cell lines manifested tumorigenic properties.

Transplantation of “benign” cervical tissues produced mucoepidermoid cysts in isologous recipient mice. Transplantation of induced early cervical carcinomas resulted in development of malignant tumors. Transition from squamous cell carcinoma to a sarcomatoid tumor was observed upon successive subcutaneous passages of one of these neoplasms.

The immediate capability of epithelial cells to establish long-term tissue culture cell lines appears early during neoplastic progression. It is an independent characteristic which should be distinguished from their tumor-forming abilities. The tumor-forming abilities of the induced cervical lesions appeared later and were demonstrable only by direct transplantation technic. Transplantation was useful in revealing tumor-forming abilities of early invasive carcinoma. It was not helpful in detecting intraepithelial carcinoma unless ample latency period was allowed for further progression of the lesions.

Results of the comparison of neoplastic progression under in vivo and in vitro conditions suggest that coexistence of epithelial cells and fibroblasts may play an important role in the phenomena of “transformation” and in the capability of “transformed” epithelial cells to develop malignant neoplasms. Further study of epithelial-mesenchymal relationship in neoplastic progression in necessary.

1

Presented at the 15th Annual Meeting of American Society of Cytology October 21, 1967, Denver, Colorado.

2

This study was supported by USPHS Grant #RO1CA 08050-03 PTHB.

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