# FIBROBLAST TUMOR CELL INTERACTIONS IN TUMOR INVASION

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1988 · $20,823

## Abstract

Degradation of extracellular matrices during tumor invasion and, in
particular, the involvement of collagenolytic enzymes, has been documented
in this and other laboratories.  Recent studies have focused on the role of
host fibroblast-tumor cell interactions in regulation of collagenase
activity and have shown that:  (1)\tumor cells produce a factor which
dramatically stimulates collagenase production by fibroblasts; (2)\the
stimulatory factor is present at the tumor cell surface; (3)\the factor can
be extracted from cell membranes by detergent; (4)\it is hydrophobic in
nature, i.e., it can be reintercalated into lipid vesicles; and (5)\the
appearance of the tumor cell factor in conditioned medium is enhanced by
exposure of the tumor cells to matrix deposited by fibroblasts.  Based on
these observations, it is proposed that the factor contains a hydrophobic
domain which is attached directly to the tumor cell plasma membrane and a
hydrophilic domain containing the active site which interacts with a
receptor on the fibroblast surface, causing stimulation of collagenase
production.  Under certain conditions, e.g., exposure to fibroblast matrix,
the hydrophilic domain would be cleaved from the tumor cell plasma membrane
and appear in conditioned medium.

Thus, a detailed investigation of the regulation of collagenase production
by fibroblast-tumor cell interactions is intended.  Fibroblasts and human
tumor cells will be used to:  (1)\generate monoclonal antibodies to the
tumor cell factor and use these to develop a sensitive assay and to purify
the factor; (2)\examine the relationship between membrane-bound and soluble
forms of the factor; (3)\study the lipophilic properties of the
membrane-bound factor; and (4)\begin a study of its interaction with
putative receptors on the fibroblast surface.  These experiments will lead
in the future to a detailed investigation at the molecular level of
regulation of factor production in tumor cells, its effect on fibroblast
collagenase production, and its role in the invasive properties of tumor
cells.  This knowledge will aid in our understnding of the metastatic
process and thus the development of therapeutic techniques.  (W)

## Key facts

- **NIH application ID:** 3177157
- **Project number:** 3R01CA038817-03S1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** CHITRA BISWAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $20,823
- **Award type:** 3
- **Project period:** 1985-07-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177157

## Citation

> US National Institutes of Health, RePORTER application 3177157, FIBROBLAST TUMOR CELL INTERACTIONS IN TUMOR INVASION (3R01CA038817-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177157. Licensed CC0.

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