The possible role of factor H in colon cancer resistance to complement attack.
A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian- and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process.
Wilczek
Ewa
E
Department of Pathology, The Medical University of Warsaw, Warsaw, Poland.
Rzepko
Robert
R
Nowis
Dominika
D
Legat
Magdalena
M
Golab
Jakub
J
Glab
Marta
M
Gorlewicz
Adam
A
Konopacki
Filip
F
Mazurkiewicz
Michal
M
Sladowski
Dariusz
D
Gornicka
Barbara
B
Wasiutynski
Aleksander
A
Wilczynski
Grzegorz M
GM
D000230:Adenocarcinoma / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D051056:Complement Inactivating Agents / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D051056:Complement Inactivating Agents; D012333:RNA, Messenger; D017242:Complement Factor H