title: SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway.
abstract: 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.
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Graduate Program, The Catholic University of America, Washington, DC, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lopez-Coral
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA; Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Germany; Department of Dermatology, Regensburg University Medical Center, Regensburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roesch
authors.affiliation: Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Cancer Biology, Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Alexander
authors.affiliation: Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Germany; Department of Dermatology, Regensburg University Medical Center, Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.affiliation: Department of Pathology and Laboratory Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hwang
authors.affiliation: Undergraduate Program, University of the Sciences, Philadelphia, Pennsylvania, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lieu
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Belser
authors.affiliation: Undergraduate Program, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Russel E
authors.initials: RE
authors.lastname: Kaufman
mesh_terms: D019011:Antigens, CD7 / Q000378:metabolism*; D017209:Apoptosis; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002630:Chemotactic Factors / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000737:chemistry; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000737:chemistry; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D019011:Antigens, CD7; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016898:Interferon-alpha; D008024:Ligands; D008565:Membrane Proteins; D061988:Proteasome Inhibitors; C111200:SECTM1 protein, human; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases