A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma

Takenaga, Mitsuko; Tamamura, Hirokazu; Hiramatsu, Ken; Nakamura, Natsumi; Yamaguchi, Yoko; Kitagawa, Aki; Kawai, Shinichi; Nakashima, Hideki; Fujii, Nobutaka; Igarashi, Rie

doi:10.1016/j.bbrc.2004.05.155

Cited by 97 publications

(79 citation statements)

References 35 publications

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“…Although preliminary, the present findings could have several therapeutic implications, including a better targeting of patients who could benefit from the adjuvant use of bone-targeting agents, including bisphosphonates [3] and RANK-or RANKL-targeting agents [4]. In addition, our data provide some arguments that the use of CXCR4 inhibitors [29,30] could lead to a lower incidence of bone metastasis in this patient population.…”

Section: Discussionmentioning

confidence: 58%

CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence

et al. 2009

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After completing this course, the reader will be able to:1. Assess CXCR4 expression in the primary tumor for use as an indicator of a higher risk for bone metastasis in early breast cancer.2. Evaluate the relationship between CXCR4 expression and the occurrence of metastases in other SDF-1-producing organs, including the liver and lung.3. Use CXCR4 in different ways in combination with other markers to identify patients to be screened for bony metastases and/or treated preventatively for bone metastasis.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTBackground. Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to eval-

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Section: Discussionmentioning

confidence: 58%

CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence

et al. 2009

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“…Some antagonist peptides in microcapsules have been tested in in vivo studies demonstrating antimetastatic activity in murine models (42). The identification of new peptides with stronger CXCR4 antagonistic activities have recently been described (43,44).…”

Section: Discussionmentioning

confidence: 99%

Human Melanoma Metastases Express Functional CXCR4

Scala

Giuliano

Ascierto

et al. 2006

Clinical Cancer Research

116

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Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1and -2 (Erk-1and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 Amol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.The incidence and mortality rate of melanoma have increased in the last 30 years. The National Cancer Institute Surveillance, Epidemiology, and End Results database documents increases of 619% in annual diagnoses of cutaneous melanoma and of 165% in annual mortality from 1950 to 2000 (1). Metastatic spread may arise from very small tumor masses and in about two-thirds of all cases of malignant melanoma, spreading develop primarily as locoregional metastases. In about onethird of the cases, primary development of distant metastases is observed (2). The metastatic potential of primary melanoma is considerably higher than that of other primary solid tumors when comparing the size of primary lesion. The usual outcome for patients with distant metastases remains bleak, with median survival of 6 to 10 months and <5% of patients surviving for >5 years (1). Except for high-dose IFN as adjuvant therapy in stage III disease, little success has emerged over the last 20 years for metastatic melanoma (3). The underlying molecular events that explain malignant melanoma genesis and progression have been only partially characterized, and only a small number of genes have been identified as playing key roles in melanoma. Among these, some cell cycle regulators, apoptotic, signal transduction, cell adhesion, and matrix digestion genes have been shown to be deregu...

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“…The efficacy of T140 and its analogs for blocking CXCR4 in vitro and in vivo has been documented in numerous preclinical studies, including in vivo models for breast cancer and melanoma, 73,74 rheumatoid arthritis 75 and stem cell mobilization. 36 Other studies explored the activity of these agents in acute 76,77 and chronic leukemias, 54 multiple myeloma, 78 small cell lung cancer (SCLC), 50 malignant melanoma 74 and pancreatic cancer.…”

Section: Small Peptide Antagonist Of Cxcr4mentioning

confidence: 99%

“…36 Other studies explored the activity of these agents in acute 76,77 and chronic leukemias, 54 multiple myeloma, 78 small cell lung cancer (SCLC), 50 malignant melanoma 74 and pancreatic cancer. 79 Besides these disease-oriented studies, T140 and its analogs have been used in basic studies exploring the function of CXCR4 in dendritic cell development 80 and migration, 81 B-cell homing and germinal center positioning within lymphatic tissues, 82 and HSC homing.…”

Section: Small Peptide Antagonist Of Cxcr4mentioning

confidence: 99%