El tejido adiposo renal humano induce la invasión y progresión del carcinoma de células renales

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.

本研究评估了源自肾细胞癌（RCC）患者肿瘤近侧（hRATnT）或远离肿瘤（hRATfT）的人体脂肪组织条件培养基（CMs）对肿瘤（786-O和ACHN）和非肿瘤（HK-2）人肾上皮细胞系增殖、粘附和迁移的影响。人体脂肪组织来自肾细胞癌患者，hRATnT和hRATfT的CMs通过培养获得。在786-O、ACHN和HK-2细胞系中，分别与hRATnT-CMs、hRATfT-CMs或对照组CMs共培养，以量化增殖、粘附和迁移。我们对hRATnT和hRATfT的CMs中的versican、脂联素和瘦素表达进行了评估。此外，我们还评估了在CMs培养的细胞系上AdipoR1/2、ObR、pERK、pAkt和pPI3K的表达。结果显示，经CMs处理24小时后，细胞系的增殖没有差异。所有细胞系在hRATnT-CMs培养后与hRATfT-CMs或对照组CMs相比，均表现出显著的粘附降低和迁移增加。与hRATfT-CMs相比，hRATnT-CMs显示出versican和瘦素水平升高。与对照组CMs相比，786-O和ACHN细胞中的AdipoR2在hRATfT-CMs和hRATnT-CMs培养后显著降低。在HK-2、786-O和ACHN细胞中，hRATnT-CMs处理导致pAkt表达降低，这一结果可能部分解释了观察到的迁移和细胞粘附的改变。我们得出结论，hRATnT释放的因子，如瘦素和versican，可能增强肾上皮细胞系的侵袭性，并可能调节疾病的进展。