Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung.

Abstract:

:The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Yan HH,Pickup M,Pang Y,Gorska AE,Li Z,Chytil A,Geng Y,Gray JW,Moses HL,Yang L

doi

10.1158/0008-5472.CAN-10-0706

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

6139-49

issue

15

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-10-0706

journal_volume

70

pub_type

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