Secretion of autocrine growth‐promoting activity by renal‐carcinoma cells treated with 5‐fluorouracil

Dysregulated cell motility is one of the major characteristics of invasion and metastatic potentials of malignant tumor cells. Here, we examined the hepatocyte growth factor (HGF)-induced cell motility of two human renal carcinoma cell lines, ACHN and VMRC-RCW. Scattering and migration was induced in ACHN in an HGFdependent manner, whereas they were maintained in VMRC-RCW even in the absence of HGF. In VMRC-RCW, HGF receptor (HGFR) tyrosine kinase was constitutively active, and sequence analysis showed N375S, A1209G and V1290L mutations. However, transfection experiments using porcine aortic endothelial (PAE) cells demonstrated that no single mutation or combination of two or three mutations caused HGFindependent constitutive activation. Conversely, the expressed amount of receptor protein had a pivotal role in the basal kinase activity. With respect to downstream signaling molecules of HGFR in ACHN or VMRC-RCW, the Ras-MAPK pathway was downregulated, whereas phosphoinositide 3-kinase (PI3-kinase) was not further activated by HGF-treatment in VMRC-RCW cells. The PI3-kinase inhibitors, wortmannin and LY294002 strongly inhibited spontaneous migration of VMRC-RCW. One transfected PAE cell line with massive overexpression of HGFR demonstrated scattered morphology and increased PI3-kinase activity in association with increased motility, which was partially inhibited by LY294002. Taken together, our results indicate that the overexpression of HGFR causes increase in cellular motility and PI3-kinase shows the important contribution on the increased motility of renal carcinoma cells. Oncogene (2001) 20, 7610 ± 7623.

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“…Human renal carcinoma cells, denoted ACHN cells and VMRC-RCW cells (Nishimura et al, 1992), were maintained …”

Section: Cell Culturementioning

confidence: 99%

Increase in hepatocyte growth factor receptor tyrosine kinase activity in renal carcinoma cells is associated with increased motility partly through phosphoinositide 3-kinase activation

et al. 2001

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“…Nishimura et al [40] also looked at the autoproliferative activity of human renal-carcinoma cells. They took the conditioned-medium superuatant of three different renal-cancer cell lines (ACHN, VMRC-RCW, and NT) to test 5-fluorouracil (5-FU), Without 5-FU, the supematant showed almost no activity for stimulating DNA synthesis.…”

Section: Laboratory Investigationmentioning

confidence: 99%

“…They took the conditioned-medium superuatant of three different renal-cancer cell lines (ACHN, VMRC-RCW, and NT) to test 5-fluorouracil (5-FU), Without 5-FU, the supematant showed almost no activity for stimulating DNA synthesis. When the line was cultured in the presence of 5-FU, the supernatant strongly exhibited the autocrine growth-promoting activity of the three cell lines in a dose-dependent manner [40]. This autocrine activity may be one 1 reason why this tumor is resistant to many anticancer agents, and it suggests that although certain agents may inhibit certain cancers, they may actually stimulate other cancers, such as renal-cell carcinoma.…”

Section: Laboratory Investigationmentioning

confidence: 99%

Growth factors and renal cancer: characterization and therapeutic implications

1995

World J Urol

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The heterogeneiety renal-cell carcinoma can lead to unpredictable behavior: the ability to achieve a large volume yet not metastasize, the ability to demonstrate late recurrence or spontaneous regression, or the capability to metastasize at a relatively small volume. One-third of all patients who undergo radical nephrectomy for presumed localized disease will eventually have metastasis. Since renal-cell carcinoma is not significantly radio- or chemosensitive, it is important to investigate new avenues for treatment of this tumor once it has spread, specifically at the molecular level. This review discusses the most recent work on growth factors and renal cancer and proposes possible modalities for treatment.

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“…7,8 For example, Nishimura et al 7 reported that three cell lines of renal cell carcinoma (ACHN, VMRC-RCW, and NT) secreted a factor(s) with autocrine growth-promoting activity in response to treatment with 5-fluorouracil. Emoto et al 8 reported that basic fibroblast growth factor secreted by VMRC-RCW cells stimulated the growth of cells in an autocrine or paracrine manner.…”

Section: Introductionmentioning

confidence: 98%

Expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in a human renal cell carcinoma cell line, VMRC-RCW

Takahashi

Totsune

Murakami

2001

Clinical and Experimental Nephrology

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Background. The kidney produces and secretes various vasoactive peptides, such as endothelin-1 and adrenomedullin, and expresses receptors for these peptides. These vasoactive peptides are considered to have autocrine or paracrine growth-regulatory activities in the kidney, in addition to actions in the renal circulation, and water and electrolyte transport. It was reported that renal cell carcinoma cell lines, such as VMRC-RCW cells, secreted some autocrine growth factors. The production of these peptides by VMRC-RCW cells has not been studied, however. Methods. We studied the expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in VMRC-RCW human renal cell carcinoma cells by radioimmunoassay, Northern blot analysis, and reverse transcriptase polymerase chain reaction (RT-PCR). Results. Northern blot analysis showed the expression of adrenomedullin mRNA in VMRC-RCW cells. RT-PCR analysis showed the expression of urotensin-II and endothelin-1 mRNAs in VMRC-RCW cells. Immunoreactive adrenomedullin and immunoreactive endothelin were detected in the culture medium (17.5 Ϯ 0.70 fmol/10 5 cells per 24 h, and 0.75 Ϯ 0.03 fmol/10 5 cells per 24 h, respectively, mean Ϯ SEM; n ϭ 6). The adrenomedullin levels in the medium were higher in VMRC-RCW cells than in DLD-1 colonic carcinoma cells and HeLa cervical cancer cells, but the endothelin levels were lower in VMRC-RCW cells. Reverse-phase high performance liquid chromatography suggested that VMRC-RCW cells secreted both endothelin-1 and endothelin-2. On the other hand, no significant amount of urotensin-II was detected in the culture medium (Ͻ0.5 fmol/10 5 cells per 24 h).Conclusions. VMRC-RCW human renal cell carcinoma cells express three vasoactive peptides; urotensin-II, adrenomedullin, and endothelin-1. The secreted peptides may be related to tumor biology as well as renal pathophysiology.

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Secretion of autocrine growth‐promoting activity by renal‐carcinoma cells treated with 5‐fluorouracil

Cited by 8 publications

References 12 publications

Increase in hepatocyte growth factor receptor tyrosine kinase activity in renal carcinoma cells is associated with increased motility partly through phosphoinositide 3-kinase activation

Increase in hepatocyte growth factor receptor tyrosine kinase activity in renal carcinoma cells is associated with increased motility partly through phosphoinositide 3-kinase activation

Growth factors and renal cancer: characterization and therapeutic implications

Expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in a human renal cell carcinoma cell line, VMRC-RCW

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