CDB15:0001536 VCAN — TLR2

Experimentally validated in Mouse; Orthology-inferred in Human, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis.

Nature, 2009; PubMed, Mus Musculus Vcan — Mus Musculus Tlr2

ABSTRACT: Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) through activation of the Toll-like receptor (TLR) family members TLR2 and TLR6. Both TNF-alpha and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC-conditioned medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer, as a macrophage activator that acts through TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth.

Basic Information on VCAN

Ligand Name: versican

Other Symbols: CSPG2, PG-M

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: VCAN

GeneCards: VCAN

HGNC Gene Group: Sushi domain containing, C-type lectin domain containing, Proteoglycans, Immunoglobulin superfamily domain containing

Functional Annotations for VCAN

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for VCAN

VCAN — CD44 ・ VCAN — ITGB1 ・ VCAN — SELP

Basic Information on TLR2

Receptor Name: toll like receptor 2

Other Symbols: TIL4, CD282

Receptor Location: cell membrane based on hpa, perplexity

HGNC Gene Symbol Report: TLR2

GeneCards: TLR2

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR2

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for TLR2

BGN — TLR2 ・ HSP90B1 — TLR2 ・ RNASE2 — TLR2 ・ SFTPA1 — TLR2 ・ ZG16B — TLR2 ・ ANXA2 — TLR2 ・ DCN — TLR2 ・ PRG4 — TLR2 ・ CCN1 — TLR2 ・ HMGB1 — TLR2 ・ HSPA1A — TLR2 ・ S100A8 — TLR2 ・ SAA1 — TLR2 ・ SFTPA2 — TLR2 ・ SFTPD — TLR2 ・ WNT5A — TLR2