Naturally produced extracellular matrix inhibits growth rate and invasiveness of human osteosarcoma cancer cells.
Enhanced supplementation with certain naturally occurring nutrients and vitamins has been associated with a reduction in occurrence and progression of human cancer. The exact mechanisms of this action are still under investigation. Extracellular matrix (ECM) plays a key role in the development of cancer. Therefore, we studied whether nutrients could exert anticancer effects through alteration of ECM biological properties. Confluent cultures of normal human dermal fibroblasts were allowed to produce and deposit ECM during a 7 d incubation period in the presence of tested compounds. Subsequently, fibroblasts were removed and the growth rates of freshly placed cultures of human osteosarcoma cells (lines U2-OS, MMNG, or SK.ES1) on pre-formed ECM were assayed in plain cell growth medium. In addition, ECM was deposited by fibroblasts on the upper surface of a porous plastic membrane and the subsequent migration of osteosarcoma cells to the other side was assayed in non-supplemented medium. The results demonstrated that the ECM produced by normal fibroblasts treated with a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea polyphenols significantly reduced the growth rate and invasive activity of osteosarcoma cells in contrast to the non-supplemented control. The changes in ECM properties were accompanied by significant changes in ECM protein and glycosaminoglycan composition as assayed immunochemically. We conclude that anticancer effects of nutrients involve beneficial changes in ECM biological properties. The role of ECM components in ECM-dependent regulation of tumor cell activities is discussed.
Ivanov
V
V
Cancer Division, Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
Ivanova
S
S
Roomi
M W
MW
Kalinovsky
T
T
Niedzwiecki
A
A
Rath
M
M
D000596:Amino Acids / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D028241:Camellia sinensis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000627:therapeutic use
D000596:Amino Acids; D010936:Plant Extracts; C465546:green tea extract AR25; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D001205:Ascorbic Acid