Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines

Russell, R. M.; Pedersen, AN; Kantor, Jason D.; Geisinger, Kim R.; Long, Rena; Zbieranski, Nora; Townsend, Alan J.; Shelton, Brent J.; Brünner, Nils; Kute, TE

doi:10.1038/bjc.1998.566

Cited by 55 publications

(43 citation statements)

References 33 publications

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“…Eight di erent genes of this family have been identi®ed in humans (Lombardi et al, 2000), and their expression is linked to suppression of tumour metastasis, di erentiation, apoptosis, proliferation and DNA mutation (de la Rosa et al, 1995). NM23-H1 and -H2 are nucleoside diphosphate (NDP) kinases, and metastasis suppression was observed in several tumour cell lines transfected with nm23-H1 (Leone et al, 1991;Russell et al, 1998). Recently, it was reported that increased nm23-H1 expression, induced by an inhibitor of DNA methylation, reduced cell motility but had little e ect on cell proliferation (Hartsough et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

et al. 2001

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PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly ampli®ed in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired a nity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found ampli®cation of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant ®brous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE ampli®cation was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE ampli®cation developed metastases. A similar situation was observed in all breast carcinomas with ampli®cation of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, ampli®-cation and overexpression of PRUNE has the same e ect in the tumours. We suggest that ampli®cation and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that a ect the development or progression of these tumours. Oncogene (2001) 20, 6881 ± 6890.

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Section: Introductionmentioning

confidence: 99%

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

et al. 2001

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“…Therapies that specifically target metastatic suppressors are expected to suppress metastasis at a toxicity lower than that of conventional chemotherapies. 2 There are a number of metastatic suppressor candidates, such as intercellular communication factors (e.g., NM23-H1/H2, 3,4 KISS1, 5 and RHOGDI2 6 ), cell surface proteins and receptors (e.g., KAI1 [CD82] 7 ), and transcription factors (e.g., LSD1…”

Section: Introductionmentioning

confidence: 99%

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Nishida-Aoki¹,

Tominaga²,

et al. 2017

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Metastasis is the main cause of cancer mortality for many types of cancer; however, difficulties remain in effectively preventing metastasis. It has been recently and widely reported that cancer-derived extracellular vesicles (EVs) contribute to cancer metastasis. Thus, therapeutic strategies targeting cancerderived EVs hold great promise because of the possibility of EVs driving the cancer microenvironment toward metastasis. Here, we provide a novel strategy for therapeutic antibody treatment to target cancer-derived EVs and inhibit the metastasis of breast cancer in a mouse model, establishing a rationale for further clinical investigation. Treatment with human-specific anti-CD9 or anti-CD63 antibodies significantly decreased metastasis to the lungs, lymph nodes, and thoracic cavity, although no obvious effects on primary xenograft tumor growths were observed. In in vitro and in vivo experiments, the EVs incubated with the targeted antibodies were preferentially internalized by macrophages, suggesting that antibody-tagged cancer-derived EVs would be eliminated by macrophages. Our results suggested that therapeutic antibody administration effectively suppresses EV-triggered metastasis in cancer and that the removal of EVs could be a novel strategy for cancer therapy.

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“…11 In the case of human ovarian cancer, nm23 is related to the lymphatic dissemination of tumor cells and its expression has been suggested to be an independent prognostic factor. 2,12,13 Several experiments have shown that the exogenous expression of human nm23H1 results in a significant reduction of metastatic potential in vivo and impairment of cell migration ability in response to several cytokines in vitro. 2,8,13 Transfection of nm23 cDNA into metastatically competent breast carcinoma, 2,12,13 melanoma, 7,[14][15][16] colon carcinoma, 17 and oral squamous cell carcinoma cell lines 18 resulted in 40-98% decreased metastatic potential in vivo.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model

Zhou

Chen

et al. 2005

Cancer Gene Ther

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Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. A cell line of high metastatic potential, SW626-M4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. Liver metastasis and animal survival time were measured after transfer of a recombinant adeno-associated viral vector expressing nm23H1 (AAV-nm23H1) into the aforementioned model. Intraperitoneal injection of AAV-nm23H1 into this orthotopic implantation model of ovarian cancer resulted in (1) expression of the exogenous gene in more than 95% of tumor cells in situ in nude mice; (2) a 60% reduction in the number of animals developing liver metastases; and (3) a 35-day prolongation of median survival time compared with the untreated host group. In conclusion, the results support the feasibility of induction of nm23H1 expression through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival time, and indicate that AAV vectors deserve attention in the design of future gene therapy approaches to achieving long-term expression of curative genes in vivo.

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Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines

Cited by 55 publications

References 33 publications

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model

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