# MALIGNANT TUMOR METASTASIS; ROLE OF VITAMIN K METABOLISM

> **NIH NIH R01** · NYSDOH/HEALTH RESEARCH, INC. · 1988 · $70,068

## Abstract

A factor X procoagulant activity occurs in some malignant tumor
types such as mouse Lewis lung(LL) carcinoma which initiates the
formation of a protective fibrin coat around cells explanted from
the primary tumor.  Warfarin, an antivitamin K drug, and dietary
induced vitamin K deficiency both dimisinh factors X
procoagulant activity in LL primary tumors and are effective in
diminishing lung metastases.  Recent data have demonstrated the
procoagulant of LL cells is not an endogenous single protease as in
rabbit V2 carcinoma, but rather its activity is dependent upon a
LL cellular component and a vitamin K-dependent protein in
serum or plasma.

The overall goals of the project are to better define the role of
procoagulant activity in metastasis and the mechanism of factor
X activation by neoplastic cells.  The specific aims are to: 1)
establish whether other neoplastic cell lines whose metastasis is
inhibited by warfarin possess a procoagulant system similar to
that of LL cells; 2) probe and identify the vitamin K-dependent
protein binding region of the cell receptor by treatment of LL
cells with various modifiers; 3) characterize the components of
the procoagulant system including the vitamin K-dependent
protein receptor and isolate them in a purified state; and 4) define
more precisely the role of procoagulant activity in cell adhesion
and growth in remote tissues.  Initially, the procoagulant systems
of Walker 256 and prostatic PAIII tumor cells will be investigated
using methods developed in this laboratory.  Functional groups of
the cell receptor will be assessed by treatment with a variety of
chemical modifying reagents and enzymes.  The identification of
the receptor will be accomplished by SDS-PAGE of selectively
radiolabeled membrane components.  Isolation of the procoagulant
components will be accomplished by affinity, immunoaffinity and
conventional chromatographic techniques.  The effects of
procoagulant activity on tumor adhesion and growth will be
determined by i.v. injection of LL cells containing various levels
of the vitamin K-dependent protein and subsequent quantitation
of lung colony formation.

Results from these investigations will enhance existing knowledge
of the mechanisms involved in vitamin K and warfarin inhibition
of tumor metastasis and permit the rational design of more
effective therapeutic approaches which will not suffer the
bleeding complications presently associated with warfarin use.

## Key facts

- **NIH application ID:** 3173567
- **Project number:** 5R01CA036063-05
- **Recipient organization:** NYSDOH/HEALTH RESEARCH, INC.
- **SAM.gov UEI:** G9H6SUM59YC4
- **Principal Investigator:** MICHAEL J FASCO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $70,068
- **Award type:** 5
- **Project period:** 1984-01-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173567

## Citation

> US National Institutes of Health, RePORTER application 3173567, MALIGNANT TUMOR METASTASIS; ROLE OF VITAMIN K METABOLISM (5R01CA036063-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173567. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*