# PATHOBIOLOGY OF B16 MELANOMA METASTASIS

> **NIH NIH R01** · NEW YORK MEDICAL COLLEGE · 1988 · $130,397

## Abstract

Three distinct dissemination-related phenotypes have been identified in
cells of the mouse B16 melanoma:  tumorigenicity, ability to spontaneously
metastasize to lungs and other organs, and ability to form colonies in
organs following intravenous injection of cells.  From a null (tumorigenic
but nonmetastatic and noncolonizing) "progenitor" cell (clone G3), a
spontaneous metastasis model system was derived, consisting of metastatic
subclones generated by phenotypic diversification in monolayer culture
(G3.5) and within a subcutaneous tumor transplant (G3.12), a null subclone
produced by long-term culturing (G3.15), and a lung-colonizing subclone
generated within a tumor transplant (G3.26).  Despite these innate
phenotypes, all clones could express metastatic activity, at least
transiently, under various experimental conditions that resulted in
alteration of tumor growth rate; an intermediate rate seems to correlate
with metastatic behavior.  This model system, and especially clones G3.12
and G3.26, will be used in a comparative pathobiological investigation of
the hypothesis that the intratumor environment created by certain tumor
growth rates is critical for metastasis to occur, and that metastasis
results from passive dissemination of quiescent and/or hypoxic cells
through partially disrupted blood vessels and lymphatic channels within
necrotic or quasi-necrotic tumor regions.  Within viable tumor cell
populations purified from subcutaneous tumors, cell cycle kinetics will be
examined by flow cytometry, and the proportion of viable cells represented
by quiescent cells will be determined.  The proportion of radioresistant
and hypoxic tumor cells will be determined by assessment of relative tumor
cell radiosensitivity in intact tumors and by incorporation of a
radiolabeled hypoxic cell radiosensitizer, 14C-labeled misonidazole.
Localization of hypoxic cells within tumors will be achieved by
autoradiography, and necrotic tumor regions, including affected blood
vessels, will be quantitated morphometrically.  The integrity of intratumor
blood vessels will be determined by morphometric analysis of tumors
perfused with india ink tracer and by examination of vascular casts of
tumors.  During initial metastatic dissemination to the lungs, the
approximate numbers of viable tumor cells entering the lungs, and the
relative timing of that dissemination, will be monitored by excising and
culturing the lungs at various intervals during subcutaneous tumor
progression.

## Key facts

- **NIH application ID:** 3170139
- **Project number:** 5R01CA032134-06
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **SAM.gov UEI:** WK63UJ11C2H7
- **Principal Investigator:** CHRISTOPHER W STACKPOLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $130,397
- **Award type:** 5
- **Project period:** 1982-05-01 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170139

## Citation

> US National Institutes of Health, RePORTER application 3170139, PATHOBIOLOGY OF B16 MELANOMA METASTASIS (5R01CA032134-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170139. Licensed CC0.

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