title: Low concentrations of the recombinant toxin protein rLj-RGD3 suppress TNF-α-induced human renal carcinoma cell invasion.
abstract: A hallmark of renal cell carcinoma (RCC) invasion is the degradation of the extracellular matrix (ECM) by the local production of gelatinase enzymes. Matrix metalloproteinase-9 (MMP-9)-induced cancer cell invasion is one of the pivotal steps in cancer metastasis. It has been reported that tumor necrosis factor-α (TNF-α), a regulator of MMP-9, can induce invasion in human renal carcinoma cells. Previous work in our laboratory has shown that rLj-RGD3, a recombinant RGD (Arg-Gly-Asp)-toxin protein from the buccal gland secretion of Lampetra japonica, possesses anti-tumor activity. In this study, we demonstrated that rLj-RGD3 suppressed TNF-α-induced MMP-9 secretion in 786-0 cells (human renal carcinoma cells). To investigate the regulatory effect of rLj-RGD3 on TNF-α-induced MMP-9 secretion, we pre-treated cells with rLj-RGD3. Interestingly, rLj-RGD3 had no significant effect on the constitutive secretion of MMPs. However, low concentrations of rLj-RGD3 decreased TNF-α-induced MMP-9 secretion. Functional studies revealed that rLj-RGD3 induced apoptosis and significantly inhibited the proliferation, migration, and invasion of 786-0 cells. Furthermore, the actin architecture in cells pre-treated with rLj-RGD3 was aggregated and disorganized. Our findings suggest that rLj-RGD3 may be used as a potential drug in renal cancer therapy.
authors: College of Life Sciences, Liaoning Normal University, Dalian 116021, China.
authors: Minli
authors: M
authors: Jin
authors: Rong
authors: R
authors: Xiao
authors: Jihong
authors: J
authors: Wang
authors: Xin
authors: X
authors: Liu
authors: Yu
authors: Y
authors: Liu
authors: Zhuang
authors: Z
authors: Xue
authors: Li
authors: L
authors: Lv
authors: Yuanyuan
authors: Y
authors: Zheng
authors: Qingwei
authors: Q
authors: Li
mesh_terms: D000199:Actins / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005397:Fish Venoms / Q000008:administration & dosage*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D007798:Lampreys; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009842:Oligopeptides / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D005397:Fish Venoms; D000922:Immunotoxins; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; C574387:RGD3 protein, Lampetra japonica; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9