The Desmoid Tumor Research Foundation

February 2023

Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors

Author Information

Baccalini EA (1), Renne SL (2, 3), Colombo P (2, 3), Pasqualini F (3, 4), Quagliuolo VL (1), Maria Cananzi FC (1, 3), Grizzi F (3, 4), Borroni EM (4, 5).

(1) Sarcoma, Melanoma and Rare Tumors Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, 20089, Italy, (2) Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, 20089, Italy, (3) Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, 20090, Italy, (4) Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Rozzano, Milan, 20089, Italy, (5) Department of Medical Biotechnologies and Translational Medicine, University of Milan, Segrate, 20054, Italy.

Publication

Anticancer Agents Med Chem

Summary

Background: Desmoid tumors have an extremely variable natural history. The uncertainty behind desmoid behavior reflects the complexity, which subtends its development and non-linear advancement. Apart from Wnt-?catenin mutation, estrogen receptors, and COX-2 overexpression, little is known about the ability of desmoids to grow and recur while being unable to metastasize. Several tumors have been shown to express the CXCR4/CXCR7/CXCL12 axis, whose functions are essential for tumoral development. Aims: This study aimed to investigate the expression of the CXCR4/CXCR7/CXCL12 axis in primary desmoid tumors and discuss the potential role of this key-signaling as an antiangiogenic therapeutic strategy. Method: In this study, 3 ?m-thick consecutive sections from each formalin-fixed and paraffin-embedded tissue block were treated with mouse monoclonal antibodies developed against CD34, CXCR4, CXCR7, and CXCL12. Results: Two distinct vessel populations: CXCR4+ and CXCR4- vessels, have been found. Similarly, chemokine receptor CXCR7 expression in the entire desmoid tumor series positively stained a portion of tumor-associated vessels, identifying two distinct subpopulations of vessels: CXCR7+ and CXCR7- vessels. All 8 neoplastic tissue samples expressed CXCL12. Immunohistochemical positivity was identified in both stromal and endothelial vascular cells. Compared to CXCR4 and CXCR7, the vast majority of tumor-associated vessels were found to express this chemokine. Conclusion: It is the first time, as per our knowledge, that CXCR4/CXCR7/CXCL12 axis expression has been identified in a desmoid type-fibromatosis series. CXCL12 expression by neoplastic cells, together with CXCR4 and CXCR7 expression by a subgroup of tumor-associated vessels, was detected in all desmoid tumor tissue samples examined. Since chemokines are known contributors to neovascularization, CXCR4/CXCR7/CXCL12 axis may play a role in angiogenesis in this soft-tissue tumor histotype, thereby supporting its growth.

View Abstract