Masters Theses

Date of Award

3-1981

Degree Type

Thesis

Degree Name

Master of Science

Major Professor

Robert L. Ullrich

Committee Members

Stephen Kennel, Fred Snyder

Abstract

This study was designed to characterize BALB/c lung tumors arising spontaneously or through induction by radiation or chemicals. In particular, the possible progressive relationship between benign and malignant tumors was examined.

The biological tumor characteristics examined were cell of origin, histological organization, growth, metastasis, and effects on tumor-bearing hosts. Changes in these characteristics were examined by serial transplantation of tumors and by examination of primary tumors of increasing clinical duration. The cell of origin was often difficult to ascertain because of the heterogeneity of cellular characteristics especially among adenocarcinomas. Cells which lacked specific identifying cytoplasmic inclusions, however, appeared to be morphological variants of either type II or Clara cells. Histological organization did not reflect a specific cell of origin nor did it predict the biological behavior of any given tumor upon transplanta-tion. Tumors were classified as benign or malignant based not only on histologic organization but also on other features including the number of mitotic figures, cellular pleomorphism, local invasiveness or seeding were assessed, however, tumors were more easily classified as benign or malignant. With transplantation, histological organization changed from adenomatous to papillary for benign-appearing tumors and from papillary to carcinomatous for malignant-appearing tumors.

No absolute differences in growth, metastasis, or mean survival time could be determined between adenomas and adenocarcinomas, or between spontaneous tumors and those from mice exposed to urethane, dimethylnitrosamine, or to gamma ray or neutron radiation. In general, with transplantation, tumors exhibited a decreased latency time, TD 50/30, and mean survival time, and an increased metastatic capability whether originally classified as benign or malignant. Out of a total of twenty-five transplanted tumors, only two spontaneous adenomas did not follow this pattern. Tumors of longer clinical duration did not necessarily exhibit any greater malignant character either by histological features or by neoplastic behavior following transplantation.

Since both benign and malignant tumors exhibited progressive alterations in neoplastic behavior, three cellular characteristics were examined to attempt to determine whether progression occurred in these tumors. Lamellar body formation, surfactant production and TSP-180 expression were the characteristics examined. Histologically benign primary adenomas produced progressively fewer and more aberrant lamellar body inclusions with transplantation and with increased time of clinical duration. Although some primary adenocarcinomas contained lamellar body producing cells even after one in vivotransplantation, the inclusions were aberrant in size and shape and were frequently amorphous rather than lamellar.

Three tumor lines and their in vitro counterparts were assayed for content of disaturated phosphatidylcholine, a primary component of surfactant. Even though two of these tumors contained lamellar body producing cells at the first transplant generation, none contained elevated levels of phosphatidycholine by the sixth in vivotransplant generation. It could not be determined from these limited studies whether surfactant production was lost by progression within individual tumor cells or by selection of an undifferentiated tumor cell phenotype.

Tumor surface protein, TSP-180, was present on adenocarcinoma cells, absent from normal lung or BHT stimulated lung cells, and present in only marginal amounts on adenoma cells. Further studies are needed to determine if this cell surface glycoprotein can be acquired by progression of adenoma cells.

These studies suggest that lung tumors in the BALB/c mouse may serve as good models for the study of progression. The loss of normal cell morphology and function can be monitored from the cell of origin to a tumor cell with quite malignant behavioral characteristics. Progressive changes in neoplastic behavior may be correlated both with the loss of normal markers (lamellar body formation and surfactant production) and possibly with the acquisition of a new marker (TSP-180). While progressive changes at the cellular level apparently occur in BALB/c lung tumors, the mechanisms responsible for each of these changes remains to be elucidated.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS