Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.
Aberrant TGFbeta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis through a process involving metalloproteinase activity. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGF beta 1 in tumors with Tgfbr2 deletion. The recruitment of Gr-1+CD11b+ cells into tumors with Tgfbr2 deletion involves two chemokine receptor axes, the SDF-1/CXCR4 and CXCL5/CXCR2 axes. Together, these data indicate that Gr-1+CD11b+ cells contribute to TGFbeta-mediated metastasis through enhancing tumor cell invasion and metastasis.
Yang
Li
L
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. li.yang@vanderbilt.edu
Huang
Jianhua
J
Ren
Xiubao
X
Gorska
Agnieszka E
AE
Chytil
Anna
A
Aakre
Mary
M
Carbone
David P
DP
Matrisian
Lynn M
LM
Richmond
Ann
A
Lin
P Charles
PC
Moses
Harold L
HL
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D017353:Gene Deletion; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D022423:Myeloid Cells / Q000201:enzymology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D039481:CD11b Antigen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D020782:Matrix Metalloproteinases