Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET (Nat Med, 2012, 18:883-891)

報告日期: 2012/11/13
報告時間: 16:00~16:50
報告學生: 王堉璿
講評老師: 沈孟儒
附件下載: 下載[1253-1350711671-1.pdf] 

Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET

Héctor Peinado, Maša Alecˇković, Simon Lavotshkin, Irina Matei, Bruno Costa-Silva, Gema Moreno-Bueno, Marta Hergueta-Redondo, Caitlin Williams, Guillermo García-Santos, Cyrus M Ghajar, Ayuko Nitadori-Hoshino, Caitlin Hoffman, Karen Badal, Benjamin A Garcia, Margaret K Callahan, Jianda Yuan, Vilma R Martins, Johan Skog, Rosandra N Kaplan, Mary S Brady, Jedd D Wolchok, Paul B Chapman, Yibin Kang, Jacqueline Bromberg & David Lyden

Nat Med. 2012 Jun;18(6):883-91.

Speaker: Yu-Shiuan Wang                              Date: 2012.11.13 (6:00~16:50)

Commentator: Meng-Ru Shen, MD & PhD                 Place: Room 602

Abstract

Tumor- derived exosomes play a key role in tumor metastasis by recruitment bone marrow-derived cells (BMDCs) which is involved in generate the microenvironment for tumorigenesis and metastasis, and education the bone marrow progenitors to progress pro-vasculogenic and -metastatic. However, the role of tumor-derived exosomes is not clarified.

In this study, the functional role of tumor-derived exosomes in formation of primary tumors and metastases are investigated by melanoma model and define melanoma-specific exosome signature comprised of tyrosinase-related protein-2 (TYRP2), very late antigen 4 (VLA-4), heat shock protein 70 (HSP70), HSP90 isoform and Met oncoprotein which are also increased with the stages. It shows that the levels of specific proteins within melanoma exosomes may be biomarkers for predicting disease stage, metastasis possibility. Moreover the CD45C-KITlow/+TIE2+ circulating bone marrow progenitor cells from metastatic melanoma also highly expressed MET receptor. The membrane trafficking regulator RAB27A is high expression in highly malignant melanoma cells. According to the results, it proposes a new mechanism to regulation metastatic progression and offers a new therapeutic direction in cancer metastatic process.

 

References

1. Théry, C., Zitvogel, L. & Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2, 569–579 (2002).

2. Sethi, N. & Kang, Y. Unravelling the complexity of metastasis—molecular understanding and targeted therapies. Nat. Rev. Cancer 11, 735–748 (2011).