Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides

Abstract

IntroductionChemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF).AimTo evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis.Material and methodsThe material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs).ResultsThe expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001).ConclusionsThe CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides.

Preclinical Evidence for Targeting PI3K/mTOR Signaling with Dual-Inhibitors as a Therapeutic Strategy against Cutaneous T-Cell Lymphoma

“…PF-502 inhibits migration of SS cells toward SDF-1 SDF-1 is known to chemoattract malignant lymphocytes in the skin tumor niche, to activate TORC1 signaling in these cells, and stimulate their proliferation (Chang et al, 2015;Maj et al, 2015;Narducci et al, 2006). Because PF-502 inhibits migration toward SDF-1 in chronic lymphocytic leukemia cells (Blunt et al, 2015), we wondered if it also inhibits migration in SS cells.…”

Expression of CD31 in Mycosis Fungoides

“…Recent years have brought significant progress in research on MF; however, the mechanisms of the disease development and progression are still not fully elucidated. Several lines of evidence suggest that, similarly to solid tumors, angiogenesis may play an important role in the growth and spread of MF (3)(4)(5)(6)(7)(8)(9). Angiogenesis is a multistep process of new capillaries formation from existing vascular network through the extension and branching in response to stimulation by proangiogenic factors.…”

Preliminary evidence of imaging of chemokine receptor-4 targeted PET/CT with [68Ga]pentixafor in non-Hodgkin lymphoma: comparison to [18F]FDG

“…In addition to the lymphomas included in the current study, chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia have been reported being positive on [ 68 Ga]pentixafor PET [4,[11][12][13]. In vitro studies with ow cytometry, reverse transcription-polymerase chain reaction, and immunohistochemical analysis also detected strong expression of CXCR4 in hairy cell leukemia, T cell lymphoblastic lymphoma/leukemia, Sézary syndrome, angioimmunoblastic lymphoma, and anaplastic large cell lymphoma [32][33][34][35][36][37][38][39]. The CXCR4-targeted imaging with [ 68 Ga]pentixafor in these lymphoma/leukemia needs to be further investigated.…”