Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma

Lee, Y.H; Tokunaga, Tetsuji; Oshika, Y; Suto, Ryuji; Yanagisawa, Kazuhiro; Tomisawa, Masashi; Fukuda, Hiroki; Nakano, Hirotaka; Abe, Satoshi; Tateishi, Akio; Kijima, Hiroshi; Yamazaki, Hitoshi; Tamaoki, Norikazu; Ueyama, Yoshito; Nakamura, Masato

doi:10.1016/s0959-8049(99)00073-8

Cited by 111 publications

(106 citation statements)

References 25 publications

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“…36 It has been reported that the expression of VEGF and/or ICAM-1 is correlated to the malignancy, or metastatic potential of tumors including osteosarcoma. 37,38 In our study, the mRNA levels of VEGF and ICAM-1 were significantly decreased by transfection of NF-kB decoy ODN, indicating that the metastatic potential of LM8 cells was decreased by the transfection of NF-kB decoy ODN.…”

Section: Discussionsupporting

confidence: 51%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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Nuclear factor-kappa B (NF-kB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-kB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-kB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-kB, NF-kB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by 'naked' NF-kB decoy ODN and that the activation of NF-kB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-kB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of 'naked' NF-kB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-kB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.

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Section: Discussionsupporting

confidence: 51%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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“…It is also of prognostic relevance with respect to the risk of metastasis formation (Weidner, 1995). Although expression of different VEGF isoforms is frequently observed in tumour tissues, it has been described that particularly expression of the higher molecular weight isoforms VEGF 165 and VEGF 189 correlates with high vessel counts and poor prognosis (Oshika et al, 1998;Lee et al, 1999;Tomisawa et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

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Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 1.4% of cancer-related deaths (Reis and Faria, 1994). The prognosis of RCC remains poor. One third of the patients already have metastases when first consulting the hospital. Another 30-40% of patients develop metastases after surgical excision of the primary tumour (Ravaud and Debled, 1999). RCC are radioresistant (Nieder et al, 1996) and more than 80% are chemoresistant (Mickisch, 1994). Since RCC are presumed to be immunogenic, several clinical trials are exploring the efficacy of cytokines, mainly interleukin 2 (IL2) and/or interferon-α (IFNα), and the transfer of lymphokine-activated killer cells (Hofmockel et al, 1997;Bukowski, 2000;Hoffman et al, 2000). Despite these new options, the median survival time of patients with metastatic disease still remains only 6-8 months and the overall 5-year survival rate is less than 5% (Moch et al, 2000;Motzer and Russo, 2000). Thus, there is an urgent requirement for alternative therapeutic modalities.The current strategy is to design therapeutic approaches based on specific biological features of each tumour type. These include (i) the aberrant expression of genes which can be recognized by the immune system as foreign (Pawelec et al, 1999;Wang and Rosenberg, 1999;Bremers and Parmiani, 2000); (ii) gene products related to the formation of new blood vessels (neoangiogenesis), since they are essential for tumour expansion and metastatic settlement (Harris and Thorgeirsson, 1998;Kerbel, 2000;Rosen, 2000) and (iii) the altered expression of adhesion molecules, matrix-degrading enzymes, their receptors and inhibitors, which are a further requisite of metastatic spread (Huang et al, 1997;Yu et al, 1997).Several technique enable the identification of tumour markers. Subtractive hybridization (Lamar and Palmer, 1984; Kunkel et al, 1985;Kuang et al, 1998), differential display reverse transcription-polymerase chain reaction (DD RT-PCR; Liang and Pardee, 1992) and hybridization of cDNA microarrays (reviewed in Khan et al, 1999) are frequently used to compare the expression patterns between tumour and normal tissue. Other approaches, such as serological screening (SEREX;Sahin et al, 1995) and screening of cytotoxic T lymphocyte activity against an autologous tumour cell line (De Plaen et al, 1988), are especially focused on the identification of immunogenic tumour molecules.We have described recently the successful use of SSH using matched RCC and normal kidney tissue . In this study, we randomly selected 16 genes, which by SSH appeared to be differentially expressed. Differential expression of 9 of these 16 genes could be verified by Northern blot analysis. 2 of the 9 genes appeared to be novel. From the remaining 7 genes, expression of 5 had been associated with the malignant phenotype. To substantiate that SSH is a suitable method for the identification of differentially expressed genes, we performed a SSH with an additional pair of normal renal and RCC tissue and compared the validity of SSH ...

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“…Because many of the receptors and downstream signaling molecules are tyrosine kinases [18,22], inhibitors of these kinases are a majority of the most promising anticancer drugs [4,10,21,27]. Although osteosarcoma has not been as well studied as other types of cancer, overexpression in osteosarcoma has been reported for both growth factors and their tyrosine kinase receptors, and overexpression of some of these molecules correlates with metastasis and poor survival in patients with osteosarcoma [5,8,9,15,17,20,23,28,33,36,47,49,60,65].…”

Section: Introductionmentioning

confidence: 99%

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Messerschmitt

Rettew

Brookover

et al. 2008

Clin Orthop Relat Res

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Inhibitors of specific tyrosine kinases are attractive lead compounds for development of targeted chemotherapies for many tumors, including osteosarcoma. We asked whether inhibition of specific tyrosine kinases would decrease the motility, colony formation, and/or invasiveness by human osteosarcoma cell lines (TE85, MNNG, 143B, SAOS-2, LM-7). An EGF-R inhibitor reduced motility of all five cell lines by 50% to 80%. In contrast, an IGF-1R inhibitor preferentially reduced motility by 42% in LM-7 cells and a met inhibitor preferentially reduced motility by 80% in MNNG cells. The inhibitors of EGF-R, IGF-1R, and met reduced colony formation by more than 80% in all tested cell lines (TE85, MNNG, 143B). The EGF-R inhibitor reduced invasiveness by 62% in 143B cells. The JAK inhibitor increased motility of SAOS-2 and LM7 cells without affecting colony formation or invasiveness. Inhibitors of HER-2, NGF-R, and PDGF-Rs did not affect motility, invasiveness, or colony formation. These results support the hypothesis that specific tyrosine kinases regulate tumorigenesis and/or metastasis in osteosarcoma.

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Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma

Cited by 111 publications

References 25 publications

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

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