Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis

Eiró, Noemí; Ovies, C.; Fernández-García, Belén; Álvarez‐Cuesta, César Cosme; González, Luis O.; Vizoso, F

doi:10.1007/s00403-012-1300-y

Cited by 30 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These factors result in the resistance of tumor cells to immune cell attack and in evasion from immune surveillance (Huang et al 2005). Furthermore, high TLR4 expression was recently reported to be associated with shortened relapse-free sur- vival in melanoma (Eiro et al 2013) and with disease progression in colon cancer (Wang et al 2010). Our results show that TLR4 affects melanoma cell proliferation and motility, although LPS-induced proliferation was not inhibited robustly by TLR4 knockdown.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Signaling Promotes the Migration of Human Melanoma Cells

Takazawa

Kiniwa

Ogawa

et al. 2014

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Immune cell Toll-like receptors (TLRs) recognize conserved microbial components, leading to immune and inflammatory responses. However, TLRs are also expressed in cancer cells, including melanoma cells, which express TLR2-4. TLR4 ligands have received attention as immunotherapies; therefore, we assessed the expression of TLR4 in human melanoma specimens (29 primary lesions and 28 metastatic lesions) representing different types of melanoma. A high percentage (≥ 90%) of melanoma lesions expressed TLR4, as judged by immunohistochemistry. Next, the role of TLR4 in cell proliferation and migration was assessed using the TLR4-positive (TLR4 + ) melanoma cell lines 501mel and 888mel, and TLR4-negative (TLR4 -) 928mel melanoma cells. Lipopolysaccharide (LPS), a TLR4 agonist, increased the proliferation of TLR4 + melanoma cells but not of TLR4 -928mel cells. The proliferation-inducing effect of LPS in 888mel cells was abolished by blockade of TLR4 signaling via treatment with short interfering RNA (siRNA) targeting TLR4 or myeloid differentiation primary response gene 88 (MyD88), a molecule downstream of TLR4. However, knockdown of TLR4 or MyD88 expression did not affect the LPS-induced proliferation of 501mel cells, suggesting that residual TLR4 signaling is sufficient to maintain cell proliferation. By contrast, LPS increased the migration of TLR4 + melanoma cells, and this effect was substantially inhibited by TLR4 or MyD88 knockdown. Furthermore, TLR4 knockdown decreased cell migration even in the absence of LPS, suggesting the presence of an endogenous TLR4 ligand(s) in melanoma cells. TLR4 signaling may contribute to melanoma progression, and caution should be exercised when using TLR4 ligands as adjuvant therapy for cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Signaling Promotes the Migration of Human Melanoma Cells

Takazawa

Kiniwa

Ogawa

et al. 2014

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…TLRs are a family of type I integral membrane glycoproteins, and based on its considerable homology in the cytoplasmic region, TLRs are also considered members of a larger superfamily that includes IL-1 receptors (IL-1Rs) (20). The human TLR family consists of 13 members, which are structurally characterized by the presence of a leucine-rich repeat domain in their extracellular region and a Toll/IL-1R domain in their intracellular region (21).…”

Section: Tlr7 Gln11leu Single Nucleotide Polymorphism and Susceptibilmentioning

confidence: 99%

“…Through the adaptor molecule myeloid differentiation primary response protein 88 (MyD88), TLRs activate signaling pathways that are responsible for the induction of interferon (IFN) regulatory factor, activator protein-1 and nuclear factor kappa-light-chain-enhancer of activated B cells (20,24,25). The genes induced by the activation of TLRs produce several inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, IFN-1, IL-6, IL-1 and granulocyte-colony stimulating factor (21). Different TLRs have been associated with the pathogenesis of several inflammatory and autoimmune skin diseases (26), and have gained interest in cancer research due to their role in tumor development and progression (18).…”

Section: Tlr7 Gln11leu Single Nucleotide Polymorphism and Susceptibilmentioning

confidence: 99%

TLR7 Gln11Leu single nucleotide polymorphism and susceptibility to cutaneous melanoma

et al. 2016

View full text Add to dashboard Cite

Abstract. Cutaneous melanoma is a life-threatening skin cancer. Its incidence is rapidly increasing, and early diagnosis is the main factor able to improve its poor prognosis. Toll-like receptors (TLRs) are transmembrane glycoproteins that recognize pathogen-and damage-associated molecular patterns, against which TLRs activate the innate immune response and initiate the adaptive immune response. Genetic variations of these receptors may alter the immune system, and are involved in evolution and susceptibility to various diseases, including cancer. The aim of the present study was to evaluate whether the presence of TLR7 glutamine (Gln) 11 leucine (Leu) polymorphism confers an increased susceptibility to cutaneous melanoma. For that purpose, a case-control study was performed with 182 melanoma cases and 89 controls. To highlight the possible association between the aforementioned polymorphism and the susceptibility to melanoma, 93 cases of single melanoma and 89 cases of multiple primary melanoma (MPM) were compared in the present study. Since the TLR7 gene is localized on the chromosome X, the allelic frequency of the Gln11Leu polymorphism was analyzed separately in males and females. The distribution of allele frequencies between melanoma cases and controls (P=0.245) and between single melanoma and MPM cases (P=0.482) was not significant. Therefore, the present results do not suggest an association between TLR7 Gln11Leu polymorphism and susceptibility to cutaneous melanoma. Further studies are required to analyze the influence of other TLR polymorphisms on the susceptibility to malignant melanoma and the involvement of innate immunity in this malignancy.

show abstract

“…Stwierdzili, że wysoki poziom ekspresji TLR4 związany był ze znacznie krótszym czasem przeżycia pacjentów. Autorzy ci podkreślają, że wzrost ekspresji receptora TLR4 może być nowym niekorzystnym czynnikiem prognostycznym w czerniaku złośliwym [67]. Nieczerniakowe nowotwory skóry (ang.…”

Section: Choroby Nowotworoweunclassified

The role of Toll-like receptors in skin diseases

Bacharewicz¹,

Reduta²,

Flisiak³

2014

View full text Add to dashboard Cite

StreSzczenieUkład odpornościowy wrodzony ma zdolność rozpoznawania drobnoustrojów za pośrednictwem obecnych na powierzchni komórek przez błonowych glikoprotein określanych jako receptory Tolllike (ang. Toll-like receptors -TLR). Receptory te, obecne na komórkach układu immunologicznego: makrofagach, komórkach dendrytycznych, mastocytach i określonych subpopulacjach limfocytów, pełnią ważną funkcję obronną w zakażeniach bakteryjnych, wirusowych i grzybiczych. Połą-czenie TLR z fragmentem drobnoustroju określanym jako wzorzec molekularny związany z patogenem (ang. pathogen-associated molecular pattern -PAMP) inicjuje wewnątrzkomórkowe mechanizmy prowadzące do wytwarzania cytokin prozapalnych. W zależności od rozpoznawanych ligandów TLR są klasyfikowane na podrodziny. Dotychczas opisano 13 różnych TLR u myszy i 11 u ludzi, które podzielono na TLR zewnątrzkomórkowe: TLR 1, 2, 4, 5, 6, 10, 11 oraz wewnątrzkomórko-we, zlokalizowane w endosomach: TLR 3, 7, 8, 9. Badania ostatnich lat wskazują również na ich rolę w rozwoju szeregu chorób, w tym wielu dermatoz. Występowanie TLR stwierdzono na powierzchni komórek naskórka i skóry właściwej, m.in. na keratynocytach, komórkach Langerhansa, fibroblastach, komórkach śródbłonka naczyń, a nawet na melanocytach i adipocytach. W pracy przedstawiono budowę i funkcję TLR oraz ich udział w patogenezie wybranych chorób skóry -infekcyjnych: bakteryjnych, wirusowych i grzybiczych, a także autoimmunologicznych, alergicznych oraz nowotworowych. Dokładne poznanie roli tych receptorów w rozwoju poszczególnych chorób stwarza możliwość ich wykorzystania w leczeniu schorzeń dermatologicznych. AbStrActThe innate immune system has the ability to recognize pathogens through Tolllike receptors (TLRs), which are transmembrane glycoproteins on the cell surface. These receptors present on the surface of immunological cells -macrophages, dendritic cells, mast cells and some populations of lymphocytes -play an important role in the defense against bacterial, viral and fungal infections. The connection of a Tolllike receptor with the microbial cell component known as pathogen associated molecular pattern (PAMP) induces intracellular mechanisms leading to the synthesis of proinflammatory cytokines. Depending on the kind of the recognized ligand, TLRs are classified into subfamilies. So far, 13 TLRs have been described in mice and 11 in humans. These receptors may be expressed extracellularly (TLRs 1, 2, 4, 5, 6, 10, 11) or intracellularly, located in endosomes (TLRs 3,7,8,9). Recent studies rola receptorów toll-like w chorobach skóry the role of toll-like receptors in skin diseases Joanna bacharewicz, teresa reduta, iwona Flisiak

show abstract

Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis

Cited by 30 publications

References 42 publications

Toll-Like Receptor 4 Signaling Promotes the Migration of Human Melanoma Cells

Toll-Like Receptor 4 Signaling Promotes the Migration of Human Melanoma Cells

TLR7 Gln11Leu single nucleotide polymorphism and susceptibility to cutaneous melanoma

The role of Toll-like receptors in skin diseases

Contact Info

Product

Resources

About