Discussion In the present study, we examined the capacity of GBC-SD and SGC-996 cell phenotypes and their invasive potential to participate in vessel-like structures formation in vitro, and succeeded in establishing GBC-SD and SGC-996 nude mouse xenograft models. In addition, highly invasive GBC-SD cells when grown in three-dimensional cultures containing Matrigel or type│collagen PND-1186 manufacturer in the absence of endothelial cells and fibroblasts, and poorly aggressive SGC-996 cells when placed on the aggressive cell-preconditioned matrix could all form patterned networks containing hollow matrix channels. Furthermore, we identified the existence of VM in GBC-SD nude mouse xenografts by immunohistochemistry
(H&E and CD31-PAS double-staining), electron microscopy and micro-MRA technique with HAS-Gd-DTPA. To our knowledge, this is the first study to report that VM not only exists in the three-dimensional matrixes of human gallbladder Sotrastaurin chemical structure carcinoma cell lines GBC-SD in vitro, but also in the nude mouse xenografts of GBC-SD cells in vivo, which is consistent with our previous finding [28]. PAS-positive patterns are also associated with poor clinical outcome for the patients with melanoma [12] and cRCC [13]. In
this study, we confirmed that VM, an intratumoral, tumor cell-lined, PAS-positive and patterned vasculogenic-like network, not only exists in the three-dimensional matrixes of human gallbladder carcinoma cell lines GBC-SD in vitro, but also in the nude mouse xenografts of medroxyprogesterone GBC-SD cells in vivo. It is suggested that the PAS positive materials, secreted by GBC-SD cells, maybe be an important ingredients of base see more membrane of VM. Tumor cell plasticity, which has also been demonstrated in prostatic carcinoma
[29–31], bladder carcinoma [32], astrocytoma [33], breast cancer [34–38] and ovarian carcinoma [39–41], underlies VM. Consistent with a recent report, which show that poorly aggressive melanoma cells (MUM-2C) could form patterned, vasculogenic-like networks when cultured on a matrix preconditioned by the aggressive melanoma cells (MUM-2B). Furthermore, MUM-2B cells cultured on a MUM-2C preconditioned matrix were not inhibited in the formation of the patterned networks [42]. Our results showed that highly aggressive GBC-SD cells could form channelized or hollowed vasculogenic-like structure in three-dimensional matrix, whereas poorly aggressive SGC-996 cells failed to form these structures. Interestingly, the poorly aggressive SGC-996 cells acquired a vasculogenic phenotype and formed tubular vasculogenic-like networks in response to a metastatic microenvironment (preconditioned by highly aggressive GBC-SD cells). GBC-SD cells could still form hollowed vasculogenic-like structures when cultured on a matrix preconditioned by SGC-996 tumor cells. These data indicate that tumor matrix microenvironment plays a critical role in cancer progression.