Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche (Cancer Cell, 2009, 15:35-44)

報告日期: 2009/03/27
報告時間: 17:10/18:00
報告學生: 黃晟協(英文報告)
講評老師: 賴明德
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980327-3.pdf

Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

Cancer cell 15, 35-44 (2009)

Janine T. Erler, Kevin L. Bennewith, Thomas R. Cox, Georgina Lang, Demelza Bird, Albert Koong, Quynh-Thu Le, and Amato J. Giaccia

 

Speaker: Cheng-Hsieh Huang

Commentator: Lai, Ming-Derg Ph.D

Date: 2009/03/27  (5:10 ~ 6:00 p.m)

Place: Room 602

 

 

Abstract:

  The major problem needs to be solved in cancer treatment is the metastasis of cancer cells. Most cancer mortality is caused by the tumor metastasis rather than presence of the primary tumor. The steps of the metastasis include the migration, invasion, intraversation, extraversation, and growth at the target organ. However, how the cancer cells determine the location they metastasize is still unclear. In recently study, the bone-marrow derived cells (BMDCs) had been found in the metastatic site, and played a role in facilitating tumor cells metastasis. Some reports have shown it could be influenced by VEGF-A, TGF-b, or TNF-a pathway in recruitment of BMDCs to metastatic site. However, the tumor-secreted proteins that are essential for formation of the premetastatic niche and that could potentially be targeted therapeutically are still largely unclear.

The hypoxia-inducing protein, lysyl oxidase (LOX), is an amine oxidase that crosslinks collagens and elestins in the extracellular matrix. In this study, hypoxic primary tumor cells could secrete LOX into the bloodstream and deposit in target organs such as lung, liver and brain. LOX could crosslink the collagens IV in target organs and facilitate BMDCs adhesion. Adhered BMDCs had higher MMP2 activity to make the collagen IV degradation. Degraded collagen IV acted as a chemoattractant to recruit more BMDCs, then formed the premetastatic niche. Moreover, the collagen IV peptides also would attract the tumor cells to distant organs. Therefore, LOX seems to be a therapeutic target in metastasis for cancer treatment.

 

References:

1.     VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820-827 (2005)

2.     Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J. Cell. Biochem. 88, 660-672 (2003).