Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts
(CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides
(MF), the most common type of cutaneous T-cell lymphoma, are unknown. This study sought
to characterize CAFs in MF and their cross talk with the lymphoma cells using primary
fibroblast cultures from punch biopsies of patients with early-stage MF and healthy
subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker,
and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells),
collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater
proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa
cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of
MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4
axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility.
Our data suggest that the fibroblasts in MF lesions are more proliferative than fibroblasts
in normal skin and that CAFs protect MF cells from doxorubicin-induced cell death
and increase their migration through the secretion of CXCL12. Reversing the CAF-mediated
tumor microenvironment in MF may improve the efficiency of anticancer therapy.
Abbreviations:
CAF (cancer-associated fibroblast), Doxo (doxorubicin), ECM (extracellular matrix), MF (mycosis fungoides), MF-F (fibroblast from patient with MF), MMP (matrix metalloproteinase), N-F (fibroblast from control subject), PBMC (peripheral blood mononuclear cell), XTT (Cell Proliferation Kit II)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: August 11, 2020
Accepted:
June 17,
2020
Received in revised form:
June 16,
2020
Received:
March 13,
2020
accepted manuscript published online 11 August 2020; corrected proof published online 5 December 2020Footnotes
See related commentary on pg 479
Identification
Copyright
© 2021 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
