CD44 is exposed to the extracellular matrix at invasive sites in basal cell carcinomas.
We have previously shown, by light microscopy, that the level of expression of CD44 (pan-CD44, CD44v3, CD44v5, and CD44v6) in human basal cell carcinomas is related to growth pattern and invasiveness (Br J Dermatol 1099;140:17-25). We have now studied the fine distribution of these CD44 isoforms in the same tumors using immunoelectron microscopy. Despite the strong differences in the level of expression in tumor areas with different growth patterns, CD44 was consistently found almost exclusively at intercellular surfaces, with a very strong predilection for widened intercellular pouches, ie, identical to the distribution in the normal epidermis. This prevalent distribution corroborates a role for CD44 in maintaining hyaluronan-filled spaces (J Histochem Cytochem 1998;46:241-248). However, the correlation between the presence of CD44 and the presence of such pouches was not absolute, indicating that other factors are involved as well. In contrast to the prevailing literature, we also found a weak but distinct labeling of cell surfaces facing the extracellular matrix. Interestingly, this appeared significantly elevated in the thinnest, most irregular, and usually most peripheral tumor cell strands, where it was associated with tumor cell protrusions and absence of a basal lamina. Thus, the CD44(+) protrusions were in direct contact with the extracellular matrix and apparently represented sites of invasion. The mechanisms that may contribute to a role of CD44 at these sites include binding of extracellular matrix components (notably hyaluronan) and several biologically active factors such as hepatocyte growth factor/scatter factor and matrix metalloproteinase 9.
Dingemans
Koert P
KP
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. k.p.dingemans@amc.uva.nl
Ramkema
Marja D
MD
Pals
Steven T
ST
D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000648:ultrastructure; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D009361:Neoplasm Invasiveness / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000648:ultrastructure
D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid