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: Tao Wang, Yingbin Ge, Min Xiao, Alfonso Lopez-Coral, Ling Li, Alexander Roesch, Catherine Huang, Peter Alexander, Thomas Vogt, Xiaowei Xu, Wei-Ting Hwang, Melissa Lieu, Eric Belser, Rui Liu, Rajasekharan Somasundaram, Meenhard Herlyn, Russel E Kaufman
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 134 Issue 4 Pg. 1108-1118 (Apr 2014) ISSN: 1523-1747 [Electronic] United States
• PMID: 24157461 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD7
• Chemotactic Factors
• Culture Media, Conditioned
• Interferon-alpha
• Ligands
• Membrane Proteins
• Proteasome Inhibitors
• SECTM1 protein, human
• Macrophage Colony-Stimulating Factor
• Phosphatidylinositol 3-Kinases

Topics

• Antigens, CD7 (metabolism)
• Apoptosis
• Cell Differentiation
• Cell Movement
• Cell Proliferation
• Chemotactic Factors (chemistry)
• Culture Media, Conditioned (chemistry)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Humans
• Interferon-alpha (metabolism)
• Ligands
• Macrophage Colony-Stimulating Factor (metabolism)
• Macrophages (cytology, metabolism)
• Melanocytes (cytology, metabolism)
• Melanoma (metabolism)
• Membrane Proteins (metabolism)
• Monocytes (cytology)
• Neoplasm Metastasis
• Phosphatidylinositol 3-Kinases (metabolism)
• Proteasome Inhibitors (chemistry)
• Protein Structure, Tertiary
• Signal Transduction