Basement membrane has a variety of effects on
tumor cells and promotes malignant behavior.
Tumor cell growth is enhanced both in vitro and in vivo in mice in the presence of basement membrane. This has led to the ability to grow various
tumors including human biopsy specimens in nude mice. Furthermore, low cell numbers can be used when coinjected with
Matrigel, a basement membrane extract. The basement membrane
glycoprotein laminin is important in promoting invasive behavior and the level of a 32/67 kDa
laminin receptor has been shown to correlate with
malignancy. A sequence of five
amino acids,
tyrosine-
isoleucine-
glycine-
serine-
arginine (
YIGSR) has been shown to recognize this receptor and to reduce experimental
metastases (tail vein injection resulting in colonization of the lung) and subcutaneous
tumor growth. This
peptide is active in both models either when coinjected or when daily
intraperitoneal injections are given after
tumor growth has initiated.
YIGSR does not effect cell arrest but does inhibit angiogenesis which is necessary for
tumor growth.
YIGSR also appears to have an additional antitumor effect via its interaction with a specific receptor.
YIGSR-adherent cells established after 30 successive selections on
YIGSR-coated dishes in vitro formed more lung colonies after
intravenous injection and larger
tumors after
subcutaneous injection than the parent B16F10
melanoma cells. The
YIGSR-non-adherent cells formed fewer lung colonies and smaller subcutaneous
tumors. These data demonstrate the importance of
laminin-
tumor cell interactions in
malignancies and suggest that a short sequence from
laminin has multiple effects in reducing
tumor growth and spread.(ABSTRACT TRUNCATED AT 250 WORDS)