Expression of RCAS1 and its function in human squamous cell carcinoma of the oral cavity.
Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a recently discovered human tumor-associated antigen expressed in a wide variety of cancer tissues. It has been suggested that tumor cells evade from immune surveillance by expression of RCAS1. We investigated whether RCAS1 is expressed in human oral squamous cell carcinomas (HOSCCs) or HOSCC (HSC-2, -3, -4, Ca9-22 and KB) cells and whether tumor cells expressing RCAS1, induce apoptosis in its receptor-positive cells, peripheral blood lymphocytes (PBLs). RCAS1 transcripts and proteins were detected in five HOSCC cell types. Immunohistochemical examinations revealed that RCAS1 was slightly to moderately positive in 32 of 40 cases (80%) of HOSCCs. Furthermore, the frequency of RCAS1 expression in HOSCC increased with advancing tumor stage according to the pTNM system. Confocal laser microscopy and DNA fragmentation assay showed that PBLs, which were stimulated with IL-2, underwent apoptosis by co-culturing with KB cells. It was also confirmed by Western dot blotting that soluble RCAS1 is secreted into culture supernatants of KB cells. The apoptotic tumor-infiltrating lymphocytes (TILs) were detected around RCAS1-positive tumor cells in HOSCCs by TUNEL method. These results suggest that RCAS1 expression might be associated with progression of oral tumors and offer a possible mechanism for oral cancer immune escape.
Fukuda
Masakatsu
M
Second Department of Oral and Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. fukudam@dent.meikai.ac.jp
Tanaka
Akio
A
Hamao
Aya
A
Suzuki
Seiji
S
Kusama
Kaoru
K
Sakashita
Hideaki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry*; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007376:Interleukin-2 / Q000378:metabolism; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000951:Antigens, Neoplasm; D017931:DNA Primers; C120762:EBAG9 protein, human; D007376:Interleukin-2; D012333:RNA, Messenger; D012313:RNA; D004247:DNA