The TNF family member APRIL promotes colorectal tumorigenesis.
The tumor necrosis factor (TNF) family member APRIL (A proliferation inducing ligand) is a disease promoter in B-cell malignancies. APRIL has also been associated with a wide range of solid malignancies, including colorectal cancer (CRC). As evidence for a supportive role of APRIL in solid tumor formation was still lacking, we studied the involvement of APRIL in CRC. We observed that ectopic APRIL expression exacerbates the number and size of adenomas in Apc(Min) mice and in a mouse model for colitis-associated colon carcinogenesis. Furthermore, knockdown of APRIL in primary spheroid cultures of colon cancer cells and both mouse and human CRC cell lines reduced tumor clonogenicity and in vivo outgrowth. Taken together, our data therefore indicate that both tumor-derived APRIL and APRIL produced by non-tumor cells is supportive in colorectal tumorigenesis.
LEXOR (Lab of Experimental Oncology and Radiobiology), Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
V
V
Lascano
L F
LF
Zabalegui
K
K
Cameron
M
M
Guadagnoli
M
M
Jansen
M
M
Burggraaf
M
M
Versloot
H
H
Rodermond
C
C
van der Loos
C E
CE
Carvalho-Pinto
H
H
Kalthoff
J P
JP
Medema
M
M
Hahne
D000818:Animals; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13