Glandular-like morphogenesis of the human submandibular tumor cell line A253 on basement membrane components.
We have studied the interaction of a human tumor cell line, A253, derived from a submandibular gland carcinoma with a differentiation promoting reconstituted basement membrane extract, Matrigel. When cultured on plastic, these cells maintain a flat, cobblestone, epithelial morphology. On Matrigel, A253 cells initially form a honeycomb network of cords of cells which subsequently thickens. With time, these cords of cells become discontinuous and blunted, whereupon multilobular clusters of cells develop. These clusters possess a lumen with polarized, PAS(+) cells containing numerous desmosomes and an abundance of glycogen. Culture of the cells on laminin, the most abundant protein found in Matrigel, also induces this morphologic differentiation. Using synthetic laminin-derived peptides, the biologically active IKVAV-containing site of laminin was most active in attachment assays, as well as in inhibiting glandular-like morphogenesis when added to the media of cells cultured on Matrigel. Antibodies to the cell surface 67- and 32-kDa laminin binding proteins partially inhibited the glandular-like morphogenesis, suggesting that multiple interactions with laminin are likely required for the differentiation process. Our data demonstrate that A253 cells can undergo glandular-like morphogenesis on basement membrane and that laminin appears to be the major initiating factor.
Kibbey
M C
MC
Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Royce
L S
LS
Dym
M
M
Baum
B J
BJ
Kleinman
H K
HK
D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008854:Microscopy, Electron; D009024:Morphogenesis; D011509:Proteoglycans / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000032:analysis; D017474:Receptors, Laminin; D013365:Submandibular Gland Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000166:cytology*
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D011971:Receptors, Immunologic; D017474:Receptors, Laminin; C059485:matrigel; D003094:Collagen