Hyaluronan mediates adhesion of metastatic colon carcinoma cells.
BACKGROUND
Hyaluronan (HA) is a cell-surface glycosaminoglycan that has been implicated in cancer progression. Cells isolated from metastatic colon carcinoma (SW620) produce greater amounts of pericellular HA than cells isolated from a primary tumor (SW480). Inhibition of hyaluronan synthases (HAS) by transfection with antisense cDNA decreases HA production. Because adhesion to the extracellular matrix (ECM) is required for invasion and metastasis, we hypothesized that pericellular HA mediates adhesion to ECM proteins such as laminin, collagen, and fibronectin and that inhibition of HA production or removal of HA by digestion with hyaluronidase would impair adhesion.


METHODS
SW480, SW620, and antisense transfectants (SW620 cells transfected with vector alone, antisense HAS2, antisense HAS3, and both antisense HAS2 and HAS3) were assessed for adhesion to laminin, Type 1 collagen, or fibronectin-coated plates. To confirm that adhesion was mediated by HA, cells were treated with or without hyaluronidase prior to the assays.


RESULTS
Metastatic SW620 cells adhered well to laminin; SW480 cells demonstrated 46% less adhesion (P < 0.05; Student's t test). SW620 cell adhesion to Type 1 collagen and fibronectin was >50% less than adhesion to laminin. Inhibition of HAS2 and/or HAS3 or pretreatment with hyaluronidase significantly decreased adhesion of SW620 cells to laminin (P < 0.05), suggesting that adhesion was dependent upon pericellular HA.


CONCLUSIONS
Metastatic SW620 cells that produce large amounts of pericellular HA adhered well to laminin. Inhibition of HAS2 and/or HAS3 expression, or hyaluronidase digestion of pericellular HA significantly inhibited adhesion. These data suggest that HA promotes adhesion to laminin and may thereby facilitate invasion of the basement membrane and metastasis in colon carcinoma.
Laurich
Chad
C
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Wheeler
Marie A
MA
Iida
Joji
J
Neudauer
Cheryl L
CL
McCarthy
James B
JB
Bullard
Kelli M
KM
D002277:Carcinoma / Q000378:metabolism / Q000503:physiopathology* / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D024042:Collagen Type I; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D005353:Fibronectins; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007797:Laminin; D008207:Lymphatic Metastasis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014166:Transferases / Q000235:genetics
D024042:Collagen Type I; D005353:Fibronectins; D007797:Laminin; D016376:Oligonucleotides, Antisense; D006820:Hyaluronic Acid; D014166:Transferases; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase