| Abstract: |
Highly differentiated epithelial populations (36% mucin-producing cells; sixfold increase in alkaline phosphatase activity; development of flat, substrate-adherent, entero-cytic foci) were induced upon in vitro exposure of HT-29di human colon carcinoma cells to sodium butyrate (NaB). 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10-7 M) and the ionophore A23187 (0.5 μM) significantly augmented (two to threefold) NaB-induced HT-29di differentiation, whereas 1,25-(OH)2D3 or A23187 alone were not effective. Induction reflected specific changes in protein abundance, involving, most notably, a differentiation-associated increase in the expression and substrate-deposition of a 47-kDa protein with pI/mw two-dimensional map coordinates and immunochemical properties identical to that of plasminogen activator inhibitor type 1 (PAI-1), a major regulator of the pericellular proteolytic cascade. Culture of HT-29di cells in medium of either high (2.5 mM) or low (0.25 mM) Ca2+ concentration did not affect the incidence of 'spontaneous' differentiation, although NaB-induced goblet cell and enterocytic maturation was Ca2+-dependent. The inability of 1,25-(OH)2D3, A23187 or modulated Ca2+ levels alone (i.e., in the absence of NaB) to effect differentiation of HT-29di cells and the Ca2+-dependence of the NaB response indicate that NaB and Ca2+ act co-operatively to induce colonic epithelial maturation in vitro. © 1994. |
| Keywords: |
controlled study; human cell; colorectal cancer; cell maturation; tumor differentiation; neoplasm proteins; cell differentiation; calcitriol; tumor cells, cultured; colorectal neoplasms; alkaline phosphatase; epithelial cells; cell count; epithelium; up-regulation; colon carcinoma; electrophoresis, gel, two-dimensional; cell adhesion; immunochemistry; plasminogen activator inhibitor 1; erythrocytes; butyric acid; goblet cell; mucin; mucins; calcium ion; butyric acids; large intestine cancer; precipitin tests; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; calcimycin; butyrate; pai-1
|
