title: Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. li.yang@vanderbilt.edu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.forename: Agnieszka E
authors.initials: AE
authors.lastname: Gorska
authors.forename: Anna
authors.initials: A
authors.lastname: Chytil
authors.forename: Mary
authors.initials: M
authors.lastname: Aakre
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Matrisian
authors.forename: Ann
authors.initials: A
authors.lastname: Richmond
authors.forename: P Charles
authors.initials: PC
authors.lastname: Lin
authors.forename: Harold L
authors.initials: HL
authors.lastname: Moses
mesh_terms: 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*
chemical_list: 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