Open AccessTLR2 and TLR4 in colorectal cancer: relationship to tumor necrosis and markers of systemic inflammation
Author(s) -
Karoliina Paarnio,
Juha P. Väyrynen,
Sara A. Väyrynen,
Tiina Kantola,
Timo Karhu,
Taina Tervahartiala,
Kai Klintrup,
Timo Sorsa,
Tuula Salo,
Jyrki M. Mäkelä,
Tuomo J. Karttunen
Publication year - 2022
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2022_220509n498
Subject(s) - tlr4 , tumor necrosis factor alpha , inflammation , systemic inflammation , proinflammatory cytokine , tlr2 , medicine , colorectal cancer , interleukin 6 , cancer , immunology , necrosis , pathology
In colorectal cancer (CRC), systemic inflammation is associated with poor prognosis, but the underlying mechanisms are not fully characterized. Tumor necrosis may contribute to systemic inflammation by inducing interleukin (IL)-6 signaling, and proinflammatory cytokines such as IL-6 and IL-8, and matrix metalloproteinase (MMP)-8 also are linked to adverse CRC outcomes. Because Toll-like receptors (TLRs) are important mediators of inflammatory responses, we investigated the roles of TLR2 and TLR4 in CRC-associated systemic inflammatory responses, especially tumor necrosis. In 118 patients with CRC, extensive tumor necrosis was associated with low TLR4 expression in tumor cells. Tumor cell TLR4 expression was inversely correlated with serum IL-6 and MMP-8 levels, blood total leukocyte and neutrophil counts, and serum C-reactive protein levels. Tumor cell TLR2 expression was not significantly associated with necrosis or systemic inflammation, but low expression in normal mucosa was linked to high serum MMP-8 and IL-8. These findings indicate that tumor necrosis is associated with low TLR4 expression in cancer cells and that low TLR4 expression correlates with a strong systemic inflammatory response. The low TLR2 expression in normal mucosa and its association with systemic inflammation suggest that the normal mucosa may reflect or contribute to the systemic inflammatory response.