Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis.
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)
Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, MD 20892.
K
K
Yamamura
M C
MC
Kibbey
S H
SH
Jun
H K
HK
Kleinman
D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000502:physiology*; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000473:pathology*; D009842:Oligopeptides / Q000737:chemistry / Q000502:physiology*; D011509:Proteoglycans / Q000737:chemistry / Q000502:physiology*; D017474:Receptors, Laminin / Q000502:physiology; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D009842:Oligopeptides; D011509:Proteoglycans; D017474:Receptors, Laminin; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; C059485:matrigel; D003094:Collagen