title: Effect of melanoma cells on proliferation and migration of activated hepatic stellate cells in vitro.
abstract: Melanoma is a highly aggressive tumor of the skin. The clinical outcome is determined by the presence or absence of metastases, and the liver is a common site of distant metastases. Hepatic metastasis is causing activation of hepatic stellate cells (HSC), which form the stroma of hepatic metastases and are increasingly recognized as a crucial component of the pro- metastatic liver microenvironment. Most studies have focused on the effects of HSC on (metastasizing) tumor cells. Here, we aimed to analyze functional in vitro effects of conditioned medium (CM) of twelve different human melanoma cell lines on LX2 cells and HSChtertcells, two well established human activated HSC cell lines. CM from melanoma cells significantly induced HSC proliferation and acted as chemoattractant for HSC in Boyden chamber assays. The CM effects significantly varied between different HSC as well as melanoma cells. Interestingly, CM from melanoma cell lines derived from melanoma metastases (WM239A, WM9, WM1158, WM1232, 451Lu and 1205Lu) had a stronger effect on proliferation of HSChtertcells than CM derived from primary melanoma tumors (SbCl2, WM3211, WM35, WM278, WM1366 and WM793). Moreover, we observed a significant correlation between the chemoattractive effects of CM from the different melanoma cells on HSChtertand LX2 cells. In contrast, the melanoma CM effects on the proliferation of the two HSC lines did not show a significant correlation. In summary, our data indicate that melanoma cells metastasizing to the liver have the potential to attract HSC and to induce HSC proliferation, respectively. Still, it appears that melanoma effects on HSC migration and proliferation are mediated via different soluble factors indicating the complexity of melanoma-HSC interaction. Furthermore, the intensity of at least some functional effects varies between different human tumor cells and HSC which may point to mechanisms explaining diverse hepatic metastasis in melanoma patients.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany; Institute for Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Eva-Vanessa
authors.initials: EV
authors.lastname: Ebert
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Czech
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Institute for Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bosserhoff
authors.affiliation: Department of Surgery, University Hospital Regensburg, Germany.
authors.forename: Sven Arke
authors.initials: SA
authors.lastname: Lang
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany; Institute for Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-University Erlangen-Nuremberg, Germany. Electronic address: claus.hellerbrand@fau.de.
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000473:pathology*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned
keywords: Hepatic stellate cells; Melanoma; Metastasis; Migration; Proliferation