ROLES OF FIBRONECTIN AND ALPHA 5 BETA 1 INTEGRIN R CELLS

Project: Research project

Project Details

Description

Extracellular matrix (ECM) proteins and their cell surface receptors
called integrins are known to play an important role in the growth,
differentiation, migration, metastasis, and invasion of cancer cells.
A number of studies have shown that decreases in expression of
fibronectin (FN) and its receptor alpha5, Beta1 intergrin, are associated
with increased malignancy in mouse transformed fibroblasts, human
neuroblastoma and carcinoma of breast, colon and pancreas. In contrast,
when alpha5,Beta1 integrin was overexpressed in tumorigenic Chinese
hamster ovary cells, they became nontumorigenic. A limited number of
studies have also suggested that interaction between ECM and integrins
may modulate growth factor action. We have observed that the expression
of FN and its receptor alpha5 subunit is cell cycle-dependent indicating
the involvement of growth factors in the control of their expression and
their possible involvement in regulating cell cycle progression. These
observations have led to the hypothesis that growth factors control the
expression of FN and alpha5 Beta1 integrin which in turn modulate the
expression and function of growth factors and their receptors to maintain
growth regulatory and tumorigenic phenotypes of human cancer cells. The
following specific aims are designed to test this hypothesis. 1. Characterization of the roles of FN and alpha5 Beta1 integrin in
conferring the phenotypes of human cancer cells (breast carcinoma MCF-7
cells, prostate carcinoma PC-3 cells, colon carcinoma Geo cells, lung
carcinoma A549 cells, fibrosarcoma HT1080 cells and glioblastoma U138
cells) with respect to their proliferation, mitogenesis, attachment,
cloning efficiency in soft agar, invasion in Matrigel, and in vivo
tumorigenicity using controlled antisense and/or sense expression
techniques. 2. Determination of the roles of FN and alpha5 Beta1 integrin in
modulating the expression and function of growth factors and their
receptors using FN and alpha5 subunit antisense and alpha5, subunit sense
transfected cells. 3. Determination of the effect of cell cycle and growth factors on the
expression of FN and alpha5 subunit at transcriptional and post-
transcriptional levels in these cancer cells. Completion of this project should benefit the assessment of using FN and
alpha5 Beta1 integrin as novel targets for tumor prevention and anti-
cancer therapy.
StatusFinished
Effective start/end date7/1/946/30/99

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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