SECTM1 Produced by Tumor Cells Attracts Human Monocytes Via CD7-mediated Activation of the PI3K Pathways
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.
Type
Journal articleSubject
MonocytesMacrophages
Melanocytes
Humans
Melanoma
Neoplasm Metastasis
Disease Progression
Macrophage Colony-Stimulating Factor
Interferon-alpha
Membrane Proteins
Antigens, CD7
Chemotactic Factors
Culture Media, Conditioned
Ligands
Signal Transduction
Apoptosis
Cell Differentiation
Cell Proliferation
Cell Movement
Gene Expression Regulation, Neoplastic
Protein Structure, Tertiary
Phosphatidylinositol 3-Kinases
Proteasome Inhibitors
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https://hdl.handle.net/10161/26515Published Version (Please cite this version)
10.1038/jid.2013.437Publication Info
Kaufman, RE (2013). SECTM1 Produced by Tumor Cells Attracts Human Monocytes Via CD7-mediated Activation
of the PI3K Pathways. J. Investigative Dermatology, 134(4). pp. 1108-1118. 10.1038/jid.2013.437. Retrieved from https://hdl.handle.net/10161/26515.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Russel E. Kaufman
Professor Emeritus of Medicine
The overall focus of this laboratory has been the study of the genetic regulation
of normal and leukemic hematopoietic cells. Hematopoietic stem cells are produced
during embryonic and fetal development and migrate to fetal liver, spleen, thymus,
and bone marrow to populate those organs for the "definitive" stages of hematopoiesis.
We initially cloned the genes that compose the beta globin gene locus and also characterized
other genomic elements that reside in and help control the e

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