Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4663
Peer-review started: July 23, 2018
First decision: August 25, 2018
Revised: October 12, 2018
Accepted: October 21, 2018
Article in press: October 21, 2018
Published online: November 7, 2018
To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC).
We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined by quantitative reverse transcription PCR (qPCR).
CD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGF-Rβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.
Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.
Core tip: Pancreatic cancer (PC) has a poor prognosis, which may partially be attributed to the abundant desmoplastic stroma, produced by cancer-associated fibroblasts (CAFs). The exact role of CAFs in PC is currently unclear, as these cells exhibited stimulation of cancer cell proliferation in vitro, but depletion of these cells promoted cancer progression in animal models. In this study, using immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization, we identified different immune phenotypic subpopulations of CAFs in PC, which may, at least in part, explain the previously published, partly contradictory data on the role of CAFs in PC. Further studies are needed to elucidate whether certain CAF subpopulations in PC have different functional properties.