# CATHEPSIN B AND TUMOR INVASION

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 1993 · $197,477

## Abstract

Cathepsin B, a lysosomal cysteine endopeptidase, has been implicated in
tumor progression, invasion and metastasis.  Increased expression (mRNA
and protein), membrane/endosomal association and release (latent and
mature forms) of cathepsin B are observed in transformed fibroblasts and
in malignant murine and human tumors, including human breast, colon,
gastric and prostate tumors.  In prostate specimens, increases in
immunostaining and in situ hybridization for cathepsin B in epithelial
cells parallel malignant progression and are observed at the leading,
invasive edges of prostate carcinomas.  The increase in mRNA and the
altered trafficking of cathepsin B in malignant cells probably reflect
modifications in more than one step in the normal pathway that leads to
the delivery of cathepsin B to lysosomes (i.e., alterations in
transcription/translation, co- or post-translational processing, and/or
in intracellular sorting and targeting).  Multiple mechanisms appear to
be responsible for the secretion of cathepsin B since both latent
precursor forms and mature forms are released.

Although membrane-associated and secreted cathepsin B have been
hypothesized to play a role in tumor invasion, there is not yet direct
evidence supporting this hypothesis.  The studies herein are designed to
determine the possible structural bases for the association of cathepsin
B with membrane/endosomal fractions and for its secretion and to provide
direct evidence for the involvement of cathepsin B in tumor cell
invasion. In the first aim of this proposal, we will continue the
biochemical characterization of tumor cathepsin B, with an emphasis on
those characteristics that could be responsible for the membrane
association and secretion of cathepsin B in malignant tumors.  The second
aim is to examine cathepsin B cDNA clones and genomic sequences from
human tumor cell lines for sequence modification.  Tumor cathepsin B will
be (over)expressed in immortal, non-tumorigenic MCF-10A human breast
epithelial cells (Aim 3) and in the poorly invasive ras-transfected
MCF-10AneoT cells (Aim 4).  These studies will determine whether
(over)expression of tumor cathepsin B affects the trafficking and
secretion of cathepsin B and/or results in acquisition or enhancement of
phenotypic properties associated with malignancy.  Properties evaluated
will include morphology, growth in low serum and soft agar, invasion,
tumorigenicity and metastatic capability.

Our working hypothesis is that increased expression of cathepsin B is one
factor leading to increases in constitutive and induced secretion of
cathepsin B in malignant cells.  Upon secretion from malignant cells,
cathepsin B can facilitate the invasion of those cells either directly by
degrading basement membrane proteins or indirectly via activating other
proteolytic enzymes.

## Key facts

- **NIH application ID:** 3174069
- **Project number:** 5R01CA036481-10
- **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:** 1993
- **Award amount:** $197,477
- **Award type:** 5
- **Project period:** 1984-02-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174069

## Citation

> US National Institutes of Health, RePORTER application 3174069, CATHEPSIN B AND TUMOR INVASION (5R01CA036481-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174069. Licensed CC0.

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