Tumour microenvironment plays a critical role in cell invasion and metastasis. To investigate the role of cancer-associated fibroblasts (CAFs) in melanoma cell invasiveness, we used 3D spheroid invasion assay. The effect of conditioned media from normal fibroblasts and CAFs cultivated alone or co-cultivated with melanoma cells on BLM or A2058 melanoma spheroid invasion was analysed. We found that conditioned media from CAFs and CAFs co-cultured with melanoma cells, especially, promote invasion and migration, without significant effect on melanoma cell proliferation. We further analysed the expression of pro-invasive cytokines IL-8 and IL-6 in media and found that melanoma cells are dominant producers of IL-8 and fibroblasts are dominant producers of IL-6 in 2D monocultures, while co-cultivation of CAFs with melanoma cells induces production/secretion of IL-6 and IL-8 into the media. The analyses of IL-6 levels in 3D cultures and human melanoma samples, however, revealed that at least in some cases IL-6 is also produced directly by melanoma cells. Analysis of the role of IL-6 and IL-8 in CAF-induced melanoma invasion, using neutralising antibodies, revealed that simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. In summary, these experiments indicate the important role of CAFs and IL-8 and IL-6 cytokines in melanoma cell invasiveness.

1st Faculty of Medicine Institute of Anatomy Charles University U Nemocnice 3 12800 Prague 2 Czech Republic

Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University Průmyslová 595 25242 Vestec u Prahy Czech Republic

Department of Cell Biology Charles University Prague Viničná 7 Prague Czech Republic

Department of Dermatovenerology 1st Faculty of Medicine Charles University and General University Hospital U Nemocnice 2 12808 Prague 2 Czech Republic

Zobrazit více v PubMed

Am J Pathol. 2012 Dec;181(6):2202-16 PubMed

Nat Cell Biol. 2007 Dec;9(12):1392-400 PubMed

Pharmacol Ther. 2014 Feb;141(2):125-39 PubMed

J Clin Aesthet Dermatol. 2014 Jun;7(6):13-24 PubMed

Biosci Rep. 2012 Feb;32(1):25-33 PubMed

BMC Biol. 2012 Mar 22;10:29 PubMed

Nutr Cancer. 2015 ;67(5):761-70 PubMed

N Engl J Med. 2012 Jan 19;366(3):207-15 PubMed

Cancer Lett. 2012 Nov 1;324(1):31-41 PubMed

Oncogene. 2016 Apr 14;35(15):1899-908 PubMed

Nat Rev Cancer. 2006 May;6(5):392-401 PubMed

Oncotarget. 2015 Dec 1;6(38):40535-56 PubMed

Biol Cell. 2012 Dec;104(12):738-51 PubMed

Int J Cancer. 2008 Mar 1;122(5):1019-29 PubMed

Cancer Med. 2012 Dec;1(3):306-17 PubMed

J Cancer. 2015 Jun 23;6(8):717-26 PubMed

Cancer Res. 2005 May 15;65(10):4134-46 PubMed

J Invest Dermatol. 2015 Dec;135(12 ):3115-3124 PubMed

FASEB J. 2007 Nov;21(13):3763-70 PubMed

Future Oncol. 2013 May;9(5):713-26 PubMed

Semin Cell Dev Biol. 2010 Feb;21(1):19-25 PubMed

Br J Cancer. 2014 Oct 14;111(8):1625-33 PubMed

BMC Cancer. 2015 Aug 13;15:584 PubMed

Tumour Biol. 2015 Aug;36(8):5873-9 PubMed

Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064-8 PubMed

Int J Cancer. 2009 Oct 15;125(8):1796-804 PubMed

Melanoma Res. 2013 Dec;23 (6):434-43 PubMed

Mol Oncol. 2014 Dec;8(8):1365-78 PubMed

Anticancer Res. 2013 Apr;33(4):1483-9 PubMed

Cancer Metastasis Rev. 2012 Jun;31(1-2):195-208 PubMed

Anticancer Res. 2015 Jun;35(6):3537-41 PubMed

Breast Cancer Res Treat. 2011 Aug;128(3):657-66 PubMed

Neoplasia. 2015 Jan;17(1):1-15 PubMed

J Immunol. 2010 Apr 1;184(7):3946-54 PubMed

Clin Cancer Res. 2014 Nov 15;20(22):5697-707 PubMed

Semin Cancer Biol. 2011 Apr;21(2):83-8 PubMed

Semin Cancer Biol. 2014 Apr;25:69-77 PubMed

Int J Cancer. 2000 Jun 15;86(6):768-76 PubMed

Am J Pathol. 2002 Jul;161(1):125-34 PubMed

Mol Cancer. 2015 Jan 05;14:1 PubMed

Biotechnol Prog. 2013 Jan-Feb;29(1):135-42 PubMed

Curr Opin Genet Dev. 2009 Feb;19(1):67-73 PubMed

J Cell Sci. 2010 Dec 15;123(Pt 24):4195-200 PubMed

Oncogene. 2014 Apr 3;33(14):1850-61 PubMed

Wound healing: insights into autoimmunity, ageing, and cancer ecosystems through inflammation and IL-6 modulation

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

Desmoplastic Crosstalk in Pancreatic Ductal Adenocarcinoma Is Reflected by Different Responses of Panc-1, MIAPaCa-2, PaTu-8902, and CAPAN-2 Cell Lines to Cancer-associated/Normal Fibroblasts

TLR4-Mediated Recognition of Mouse Polyomavirus Promotes Cancer-Associated Fibroblast-Like Phenotype and Cell Invasiveness

Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

Interleukin-6: Molecule in the Intersection of Cancer, Ageing and COVID-19

Cutaneous melanoma dissemination is dependent on the malignant cell properties and factors of intercellular crosstalk in the cancer microenvironment (Review)

Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: Pilot study

The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

Fibroblasts potentiate melanoma cells in vitro invasiveness induced by UV-irradiated keratinocytes

Microenvironment‑driven resistance to B‑Raf inhibition in a melanoma patient is accompanied by broad changes of gene methylation and expression in distal fibroblasts

Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

Intercellular crosstalk in human malignant melanoma