Title:Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors
Volume: 23
Issue: 20
Author(s): Edoardo Andrea Baccalini, Salvatore Lorenzo Renne, Piergiuseppe Colombo, Fabio Pasqualini, Vittorio Lorenzo Quagliuolo, Ferdinando Carlo Maria Cananzi, Fabio Grizzi*Elena Monica Borroni
Affiliation:
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, 20090, Italy
- Department of Immunology and Inflammation, IRCCS Humanitas
Research Hospital, Rozzano, Milan, 20089, Italy
Keywords:
Desmoid tumors, angiogenesis, chemokines, CXCR4, CXCR7, CXCL12, therapy.
Abstract:
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-
βcatenin 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.
Methods: In this study, 3 μm-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.
