title: Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells.
abstract: Although CD133 has been reported to be a promising colon cancer stem cell marker, the biological functions of CD133+ colon cancer cells remain controversial. In the present study, we investigated the biological differences between CD133+ and CD133- colon cancer cells, with a particular focus on their interactions with cancer-associated fibroblasts, especially CD10+ fibroblasts. We used 19 primary colon cancer tissues, 30 primary cultures of fibroblasts derived from colon cancer tissues and 6 colon cancer cell lines. We isolated CD133+ and CD133- subpopulations from the colon cancer tissues and cultured cells. In vitro analyses revealed that the two populations showed similar biological behaviors in their proliferation and chemosensitivity. In vivo analyses revealed that CD133+ cells showed significantly greater tumor growth than CD133- cells (P=0.007). Moreover, in cocultures with primary fibroblasts derived from colon cancer tissues, CD133+ cells exhibited significantly more invasive behaviors than CD133- cells (P<0.001), especially in cocultures with CD10+ fibroblasts (P<0.0001). Further in vivo analyses revealed that CD10+ fibroblasts enhanced the tumor growth of CD133+ cells significantly more than CD10- fibroblasts (P<0.05). These data demonstrate that the in vitro invasive properties and in vivo tumor growth of CD133+ colon cancer cells are enhanced in the presence of specific cancer-associated fibroblasts, CD10+ fibroblasts, suggesting that the interactions between these specific cell populations have important roles in cancer progression. Therefore, these specific interactions may be promising targets for new colon cancer therapies.
authors: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Lin
authors: L
authors: Cui
authors: Kenoki
authors: K
authors: Ohuchida
authors: Kazuhiro
authors: K
authors: Mizumoto
authors: Taiki
authors: T
authors: Moriyama
authors: Manabu
authors: M
authors: Onimaru
authors: Kohei
authors: K
authors: Nakata
authors: Toshinaga
authors: T
authors: Nabae
authors: Takashi
authors: T
authors: Ueki
authors: Norihiro
authors: N
authors: Sato
authors: Yohei
authors: Y
authors: Tominaga
authors: Masao
authors: M
authors: Tanaka
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000172:deficiency* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015260:Neprilysin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000172:deficiency* / Q000378:metabolism*; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D015260:Neprilysin