Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration

• DOI: 10.1038/ncomms15584
• Publication Date: 2017-05-26T10:21:49Z
• Authors: Hasini Jayatilaka; Pranay Tyle; Jonathan J. Chen; Minsuk Kwak; Julia Ju; Hyun Ji Kim; Jerry S. H. Lee; Pei-Hsun Wu; Daniele M. Gilkes; Rong Fan; Denis Wirtz
• Keywords: Science; Antineoplastic Agents; Mice, SCID; Antibodies, Monoclonal, Humanized; Article; Actin-Related Protein 2-3 Complex; Receptors, Interleukin-8A; Mice; 03 medical and health sciences; Cell Movement; Mice, Inbred NOD; Cell Line, Tumor; Paracrine Communication; Animals; Humans; Neoplasm Invasiveness; Molecular Targeted Therapy; RNA, Small Interfering; Cell Proliferation; 0303 health sciences; Interleukin-6; Q; Carcinoma; Interleukin-8; Receptors, Interleukin-6

Abstract Following uncontrolled proliferation, a subset of primary tumour cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized be the initiators metastasis. This study reveals an adaptive mechanism harnesses synergistic paracrine signalling via IL-6/8, which is amplified by cell proliferation density, directly promote migration. effect occurs in metastatic human sarcoma carcinoma cells– but not normal or non-metastatic cancer cells-, likely involves downstream WASF3 Arp2/3. The transcriptional phenotype high-density emerges due resembles low-density treated with combination IL-6/8. Simultaneous inhibition IL-6/8 receptors decreases expression Arp2/3 mouse xenograft model reduces potential promotes infers strategy decrease capacity cells.