SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway.

Journal Article

Tumor-associated macrophages (TAMs) have essential roles in tumor progression and metastasis. Tumor cells recruit myeloid progenitors and monocytes to the tumor site, where they differentiate into TAMs; however, this process is not well studied in humans. Here we show that human CD7, a T-cell and NK cell receptor, is highly expressed by monocytes and macrophages. Expression of CD7 decreases in M-CSF-differentiated macrophages and in melanoma-conditioned medium-induced macrophages (MCMI/Mφ) in comparison to monocytes. A ligand for CD7, SECTM1 (secreted and transmembrane protein 1), is highly expressed in many tumors, including melanoma cells. We show that SECTM1 binds to CD7 and significantly increases monocyte migration by activation of the PI3K (phosphatidylinositol 3'-kinase) pathway. In human melanoma tissues, tumor-infiltrating macrophages expressing CD7 are present. These melanomas, with CD7-positive inflammatory cell infiltrations, frequently highly express SECTM1, including an N-terminal, soluble form, which can be detected in the sera of metastatic melanoma patients but not in normal sera. Taken together, our data demonstrate that CD7 is present on monocytes and tumor macrophages and that its ligand, SECTM1, is frequently expressed in corresponding melanoma tissues, possibly acting as a chemoattractant for monocytes to modulate the melanoma microenvironment.

Full Text

Duke Authors

Cited Authors

  • Wang, T; Ge, Y; Xiao, M; Lopez-Coral, A; Li, L; Roesch, A; Huang, C; Alexander, P; Vogt, T; Xu, X; Hwang, W-T; Lieu, M; Belser, E; Liu, R; Somasundaram, R; Herlyn, M; Kaufman, RE

Published Date

  • April 2014

Published In

Volume / Issue

  • 134 / 4

Start / End Page

  • 1108 - 1118

PubMed ID

  • 24157461

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

International Standard Serial Number (ISSN)

  • 0022-202X

Digital Object Identifier (DOI)

  • 10.1038/jid.2013.437

Language

  • eng