Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6

Marutsuka, Kousuke; Hasui, Yoshihiro; Asada, Yujiro; Naito, Seiji; Osada, Yoshihito; Sumiyoshi, Akinobu

doi:10.1007/bf00133616

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…In addition, NF-kB signal blockade does not affect tumor cell proliferation in vitro or in vivo but prevents intravasation of tumor cells in an in vivo chick chorioallantoic membrane model of metastasis as well as spontaneous metastasis in a murine model. In SN12C-PM6, Marutsuka et al [35] have reported that the increase in plasminogen activator inhibitor 2 and the decrease in urokinase-like plasminogen activator correlate with the inhibitory effects on tumor growth and metastasis by suramin. In other type of tumor, UCH-L1 protein expression is lower in the primary tumor cell line than in the nontumor cell line of melanoma and breast cancer [30,31].…”

Section: Ubiquitin Carboxyl-terminal Hydrolase Isozyme L1 (Uch-l1 Pgmentioning

confidence: 97%

Downregulation of two isoforms of ubiquitin carboxyl‐terminal hydrolase isozyme L1 correlates with high metastatic potentials of human SN12C renal cell carcinoma cell clones

Tanaka¹,

Kuramitsu²,

Fujimoto³

et al. 2008

Electrophoresis

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Proteomic differential display analysis was performed on human renal cell carcinoma cell SN12C clones having different metastatic potentials by using 2-DE and LC-MS/MS. The SN12C cell clones were SN12C parent cell line, SN12C-clone 2, SN12C-clone 4, and SN12C-PM6. The SN12C parent cell line was established from an HRCC surgical specimen. SN12C-clone 4 has lower, and SN12C-clone 2 and SN12C-PM6 have higher metastatic potential than SN12C parent cells. We found eight protein spots whose expression level was different between low metastatic clones and high metastatic clones. The protein expression of three appeared to be higher in high metastatic clones than low metastatic clones, and that of other five protein spots appeared to be lower in high metastatic clones than low metastatic clones. These spots were selected, digested and analyzed by LC-MS/MS analysis, and they were identified by peptide sequencing tag. In high metastatic potential clones, two isoforms of ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) were downregulated. These results suggest that UCH-L1 expression seems to be associated with the metastatic potential of HRCC SN12C cell clones.

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Section: Ubiquitin Carboxyl-terminal Hydrolase Isozyme L1 (Uch-l1 Pgmentioning

confidence: 97%

Downregulation of two isoforms of ubiquitin carboxyl‐terminal hydrolase isozyme L1 correlates with high metastatic potentials of human SN12C renal cell carcinoma cell clones

Tanaka¹,

Kuramitsu²,

Fujimoto³

et al. 2008

Electrophoresis

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“…Given the poor prognosis of pancreatic cancer patients it is not surprising that there was increased expression of uPA and uPAR in fresh pancreatic cancer tissue and that over expression was related with poorer survival [29]. That uPA and its receptor uPAR can act as a target for anti-cancer therapy has been extensively documented in mouse models [30,31]. Bound to its specific cell surface receptor (uPAR), uPA efficiently converts the inactive zymogen, plasminogen, into the active serine protease, plasmin, which then cleaves either directly or indirectly extracellular matrix components including laminin, fibronectin, and collagen [26,27].…”

Section: Targeting Vectorsmentioning

confidence: 99%

Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

Allen

Rizvi

et al. 2011

Cancers

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Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro-metastatic pancreatic cancer with over-expression of MUC1 and uPA receptors in post-surgical patients with minimal residual disease. The observation of tumor regression in a Phase I clinical trial of targeted alpha therapy for metastatic melanoma indicates that alpha therapy can regress tumors by a process called tumor anti-vascular alpha therapy (TAVAT). As a consequence, this therapy could be indicated for the management of non-surgical pancreatic cancer tumors.

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“…More recently its wider potential has been investigated (Voogd et al, 1993) and it has undergone trials as an anti-cancer agent in possible treatment of metastatic cancers such as hormone refractory prostate cancer (Rago et al, 1991;Miglietta et al, 1992) and adrenocortical carcinomas (Stein et al, 1989). The ability of suramin tc inhibit cancer metastasis (Marutsuka et al, 1995) may have implications in other conditions where matrix degradation occurs. Several mechanisms of action have been proposed including inhibition of angiogenesis (Gagliardi et al, 1992) and inhibition of proteinases (Cad6ne et al, 1997).…”

Section: Introductionmentioning

confidence: 97%

The effect of suramin on the resorption of bovine nasal cartilage

et al. 1999

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Suramin is an anti-neoplastic drug. Its actions include the inhibition of binding of urokinase-type plasminogen activator (uPA) to its receptor, an event which may prevent cartilage breakdown. The aim of this work was to determine the effect of suramin on cartilage resorption. Cartilage expiants, stimulated with interleukin-1alpha, tumour necrosis factor-alpha or retinoic acid were incubated with suramin. Release of incorporated (35)S-sulphate from pre-labelled expiants was used as a measure of proteoglycan breakdown and toluidine blue staining was used to visualise proteoglycan loss.Suramin inhibited the resorption of cytokine and retinoic acid-stimulated bovine nasal cartilage at concentrations between 100-1000 microM. These findings were confirmed by histochemistry. Though reversibility studies indicated that suramin toxicity could not be excluded above 100 muM, retention of suramin in the expiants may have contributed to this. There was no significant effect on lactate production up to 500 muM. The observed inhibition of cartilage resorption may reflect actions of suramin on the PA/plasmin system or on cytokine action.

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Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6

Cited by 12 publications

References 17 publications

Downregulation of two isoforms of ubiquitin carboxyl‐terminal hydrolase isozyme L1 correlates with high metastatic potentials of human SN12C renal cell carcinoma cell clones

Downregulation of two isoforms of ubiquitin carboxyl‐terminal hydrolase isozyme L1 correlates with high metastatic potentials of human SN12C renal cell carcinoma cell clones

Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

The effect of suramin on the resorption of bovine nasal cartilage

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