The
cancer SCM-recognition, immunedefense suppression, and
serine protease protection (
CRISPP) peptide, produced by
cancer cells, is homologous to the Pn',
enzyme-baiting region of the
serine protease inhibitor alpha 1-PI. In contrast to the inhibitory function of the intact alpha 1-PI, the
CRISPP peptide protects
cancer-associated
serine proteases against inhibition by alpha 1-PI. In the presence of alpha 1-PI, the prevention of inhibition is a competitive, concentration-dependent process. The shortest fragment of the 29 amino acid sequence of the synthetic, CRISPPs
peptide, which protects
serine proteases against inhibition as efficiently as the whole molecule, encompasses the amino terminal
amino acid residues 1 to 7.
Serine proteases and their inhibitor, alpha 1-PI, are involved in the control of many intra- and extracellular physiological processes, including degradative actions in
cancer cell invasion, metastatic spread, and neovascularization of
tumors. The
CRISPP peptide protection of
serine proteases against inhibition could unbalance the regulatory controls requiring limited proteolysis by
serine proteases. The inherited and/or acquired aberrations resulting in the production of CRISPP
peptides in
cancer cells could, therefore, be one of the key factors involved in the carcinogenic transformation, enhancing uncontrolled gene derepression and
DNA synthesis, and supporting invasion and
metastasis. A hypothesis on the mechanism of
CRISPP peptide action is proposed.