Date of Award:

5-1-1992

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Department name when degree awarded

Biology/Molecular Biology

Committee Chair(s)

Lawrence H. Piette

Committee

Lawrence H. Piette

Committee

Ann E. Aust

Committee

Thomas A. Grover

Committee

Joseph K. -K. Li

Committee

Jon Y. Takemoto

Committee

Nabil N. Youssef

Abstract

Fibronectin is involved in a variety of biological events such as cellular adhesion, cell growth, wound healing, and malignant transformation. In vitro, chemically or retrovirally transformed fibroblasts show a reduced ability to assemble a fibronectin-extracellular matrix. Very little is known about mechanisms of extracellular matrix assembly and the reduced assembly mechanism during cell transformation. This study was conducted to determine the importance of fibronectin integrity in tumor promotion. C3H/10T1/2 cells and several derivatives were utilized in this study. One such derivative used is the INIT/10T1/2 cell, which is a clone of methylcholanthrene-initiated C3H/10T1/2 cells and which has been inhibited from neoplastic transformation by culturing in retinyl acetate. This cell line was reported to possess the "initiated" phase and found to be a good model to study early biochemical changes in growth control mechanisms resulting in cell transformation. Furthermore, this study was designed to yield some information regarding the mechanism(s) of the inhibitory effect of retinoids on neoplastic progression. C3H/10T1/2 and INIT/10T1/2 cells exhibit extensive fibrillar fibronectin matrix development. However, the MCA/10T1/2 cell, which was a clone of methylcholanthrenetransformed C3H/10T1/2 cells, showed poor fibronectin matrix assembly but high binding affinity to fibronectin. The high binding activity to fibronectin was also seen as one of the early changes in INIT/10T1/2 cells. Increased degradation of endogenous fibronectin was observed in MCA/10T1/2 cells as well and in prolonged culturing of INIT/10T1/2 cells. In the presence of retinyl acetate, the degradation of fibronectin was inhibited in non-transformed cells. Prolonged culturing of non-transformed cells with retinyl acetate resulted in the disorganization of the fibronectin extracellular matrix assembly. This is probably due to the inhibitory effect of retinyl acetate on fibronectin receptor processing.

Download

Share

COinS

Copyright for this work is retained by the student. If you have any questions regarding the inclusion of this work in the Digital Commons, please email us at .