# MEMBRANE ANTIGENS THAT MEDIATE METASTATIC PHENOTYPE

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1988 · $152,377

## Abstract

The plasma membrane is believed to play an important role in the successful
establishment of hematogenous metastases.  The membrane bears 1) enzymes
required for destruction of basement membrane barriers; 2) receptors for
homotypic and heterotypic cell associations; and 3) antigens which direct
specific and nonspecific immune reactivities.  The purpose of this study is
to isolate and characterize cells surface moieties that influence
metastatic phenotype, using a combination of butanol extraction,
preparative isoelectric focusing, high performance gel permeation, ion
exchange and hydrophobic interaction chromatography, and lectin affinity
chromatography.  The applicant has employed noncytolytic extraction using
butanol to enhance the incidence of experimentally-induced pulmonary
metastases.  Extraction increases the metastatic potential of sublines of
either low or high metastatic phenotype derived from the chemically induced
fibrosarcoma, MCA-F, or spontaneous melanoma, B16.  Brief incubation of
extracted cells in crude butanol extracts (CBE) or partially-purified
preparations reconstitutes the metastatic phenotype to that of the
unextracted controls.  The reconstitutive activity in partially purified
preparations is quantitatively assessed as the mg amount of protein
necessary to reduce the incidence of experimentally-induced pulmonary
metastases by 50%.  The reconstituting activity from B16-F1 displays of pI
of 546 to 5.8, a mol. wt of 15 to 30 kDa, and a specific reconstituting
activity of 10-4 U/mg.  The mechanism of reconstitution is also under
investigation.  We are currently testing the hypothesis that extraction
removes cell surface-associated protease inhibitors, resulting in a
facilitated egress of pulmonary emboli into the surrounding tissues.
Immunization of syngeneic hosts with CBE from B16-F10 prior to i.v.
challenge significantly increases the incidence of experimentally-induced
lung metastases, and this effect can be adoptively transferred using spleen
cells.  Both adherent and nonadherent splenic populations are necessary to
transfer suppression.  The final objective of this proposal is to delineate
the cellular immune response to suppressogens in CBE, and to characterize
the molecules and immune cells participating.  Thus, butanol extraction of
metastatic cells allows investigation of possible mechanisms involved in
hematogenous metastases, the role of tumor cell surface structures in
metastasis, and the effect of antigenic stimulation on the eventual
development of metastases.

## Key facts

- **NIH application ID:** 3176574
- **Project number:** 5R01CA038500-05
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** STEPHEN J LE GRUE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $152,377
- **Award type:** 5
- **Project period:** 1984-03-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176574

## Citation

> US National Institutes of Health, RePORTER application 3176574, MEMBRANE ANTIGENS THAT MEDIATE METASTATIC PHENOTYPE (5R01CA038500-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176574. Licensed CC0.

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