title: S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/gammaCnull (NOG) mouse model.
abstract: Tumor xenografts in immune-deficient mice (athymic nude mice and SCID mice) are well-established animal models for the study of human cancer. Several human melanoma cell lines were reported to metastasize in the immune-deficient mice models. However, metastatic rates were extremely low in spite of large numbers of injections of cancer cells, more than 1 x 10(6) cells/mouse. The NOD/SCID/gamma(C)(null) (NOG) mouse shows multiple immunological dysfunctions, including cytokine production capability, in addition to the functional incompetence of T, B and natural killer (NK) cells. However, the immune-deficient mice, with preserved NK cell activity, might interfere with engraftment efficiency. We examined the distant metastasis of the human melanoma cell lines (A2058, A375, G361 and HMY-1, 1 x 10(4) cells/mouse) in the 6 weeks after intravenous inoculation. All four melanoma cell lines showed metastasis in the NOG mice, while no metastatic lesions were observed in the NOD/SCID mice. Metastatic lesions were noted in the liver and lung of 6/6 (100%) mice at A2058, 8/9 (89%) at A375, 2/6 (33%) at G361 and 2/8 (25%) at HMY-1. A2058 and A375 cell lines with high metastatic potentials show increased gene expression of S100A4. Western blot assay confirmed the increased protein levels of S100A4 in the A2058 and A375 cell lines. E-cadherin gene expression was conversely inhibited in these cell lines. The increased expression of S100A4 combined with inhibited E-cadherin expression resulted in high metastatic potentials of the human melanoma cell lines in vivo.
authors.affiliation: Department of Dermatology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ikoma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Oida
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.forename: Hozumi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Ohta
authors.forename: Akira
authors.initials: A
authors.lastname: Ozawa
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011237:Predictive Value of Tests; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; D012334:RNA, Neoplasm; D018121:Receptors, Cytokine; D009418:S100 Proteins