# CATHEPSIN B-LIKE CYSTEINE PROTEINASES AND TUMOR INVASION

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 1988 · $113,429

## Abstract

Proteolytic enzymes have been implicated in invasive processes of
the metastatic cascade.  Our long term objective is to determine
the role(s) of the cysteine proteinase cathepsin B and endogenous
cysteine proteinase inhibitors (CPI) in tumor cell metastasis.  We
have purified two forms of cathepsin B (35 and 25 kDa) from
human tumors and shown their immunological relatedness to
human liver cathepsin B (25 kDa) by Western blots.  We have
shown that tumor cathepsin B's have enhanced activity against the
extracellular matrix substrate laminin at a physiologically
relevant pH (6.5).

The hypothesis that cathepsin B participates in tumor cell
extravasation during the metastatic cascade will be tested in
vitro in a series of assays which encompass the invasive process:
1) tumor cell adhesion the basement membrane, 2) tumor cell
chemotaxis during extravasation, 3) tumor cell degradation of the
basement membrane or isolated components and/or 4) tumor cell
invasion through the amnion basement membrane.  Two classes of
inhibitors of cathepsin B will be tested in these assays:
endogenous low Mr protein CPI and a series of synthetic inhibitors
screened for selectivity against the purified tumor cathepsin B's.
CPI will be purified to homogeneity from human liver and tumors.
Studies to date indicate that tumor cell chemotaxis, adhesion and
invasion are all blocked by CPI as well as by specific synthetic
inhibitors.

In murine tumors (melanoma and hepatoma) and in human breast
tumors, the subcellular distribution of cathepsin distribution of
cathepsin B is bimodal with as much as 37% of cathepsin B
activity cosedimenting with plasma membrane fractions in the
highly metastatic B16 amelanotic  melanoma (B16a) rather that
with the lysosmal fraction as in normal cells.  The 35 kDa tumor
cathepsin B may well be a precursor of mature lysosmal cathepsin
B as a 35 kDa precursor predicted from the recently isolated
cDNA clones.  One hypothesis which will be tested is that the
processing of cathepsin B in tumors may be defective.

The proposed studies should further our understanding of the role
of cathepsin B in a proteolytic cascade resulting in metastasis.  It
might be possible to interrupt this cascade by designing
therapeutic interventions to inhibit cathepsin B and/or to correct
the proposed defect in processing, i.e., direct tumor cathepsin B
to lysosmes.

## Key facts

- **NIH application ID:** 3174065
- **Project number:** 5R01CA036481-05
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **SAM.gov UEI:** M6K6NTJ2MNE5
- **Principal Investigator:** BONNIE F SLOANE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $113,429
- **Award type:** 5
- **Project period:** 1984-02-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174065

## Citation

> US National Institutes of Health, RePORTER application 3174065, CATHEPSIN B-LIKE CYSTEINE PROTEINASES AND TUMOR INVASION (5R01CA036481-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174065. Licensed CC0.

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