Ectopically expressed variant form of sperm mitochondria-associated cysteine-rich protein augments tumorigenicity of the stem cell population of lung adenocarcinoma cells.
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have self-renewal ability, differentiation ability and high tumor-initiating ability. CSCs/CICs are resistant to cancer therapies including chemotherapy and radiotherapy. Therefore, CSCs/CICs are thought to be responsible for cancer recurrence and distant metastasis after treatment. However, the molecular mechanisms of CSCs/CICs are still elusive. In this study, we isolated CSCs/CICs as side population (SP) cells from lung carcinoma, colon carcinoma and breast carcinoma cells and analyzed the molecular mechanisms of CSCs/CICs. cDNA micro-array screening and RT-PCR analysis revealed that sperm mitochondria-associated cysteine-rich protein (SMCP) is ectopically expressed in SP cells. 5'-Rapid amplification of cDNA end (RACE) analysis revealed that the SMCP transcript in SP cells was a variant form (termed vt2) which is composed from only one exon. SMCP vt2 was detected in only cancer cells, whereas the wild-type (vt1) form of SMCP was expressed in the testis. SMCP was shown to have a role in tumor initiation by SMCP overexpression and SMCP knockdown using siRNAs in lung cancer cells. Taken together, the initiation results indicate that an ectopically expressed variant form of SMCP has a role in tumor initiation of CSCs/CICs and that the variant form of SMCP might be a novel CSC/CIC marker and a potential and promising target of CSC/CIC-targeting therapy.
Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Cancer Diagnosis Laboratory, Japan Science and Technology Agency Innovation Plaza Hokkaido, Japan Science and Technology Agency, Kita-Ku, Sapporo, Japan.
Akari
A
Takahashi
Yoshihiko
Y
Hirohashi
Toshihiko
T
Torigoe
Yasuaki
Y
Tamura
Tomohide
T
Tsukahara
Takayuki
T
Kanaseki
Vitaly
V
Kochin
Hiroshi
H
Saijo
Terufumi
T
Kubo
Munehide
M
Nakatsugawa
Hiroko
H
Asanuma
Tadashi
T
Hasegawa
Toru
T
Kondo
Noriyuki
N
Sato
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells
D014408:Biomarkers, Tumor; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C484385:SMCP protein, human