The tumor microenvironment consists of stromal cells, extracellular matrix, and physicochemical properties (e.g., oxygenation, acidification).,An important element of the tumor niche are cancer-associated fibroblasts (CAFs).,They may constitute up to 80% of the tumor mass and share some features with myofibroblasts involved in the process of wound healing.,CAFs can facilitate cancer progression.,However, their interaction with melanoma cells is still poorly understood.,We obtained CAFs using conditioned media derived from primary and metastatic melanoma cells, and via co-culture with melanoma cells on Transwell inserts.,Using 2D and 3D wound healing assays and Transwell invasion method we evaluated CAFs’ motile activities, while coverslips with FITC-labeled gelatin, gelatin zymography, and fluorescence-based activity assay were employed to determine the proteolytic activity of the examined cells.,Western Blotting method was used for the identification of CAFs’ markers as well as estimation of the mediators of MMPs’ (matrix metalloproteinases) expression levels.,Lastly, CAFs’ secretome was evaluated with cytokine and angiogenesis proteomic arrays, and lactate chemiluminescence-based assay.,Acquired FAP-α/IL6-positive CAFs exhibited elevated motility expressed as increased migration and invasion ratio, as well as higher proteolytic activity (area of digestion, MMP2, MMP14).,Furthermore, fibroblasts activated by melanoma cells showed upregulation of the MMPs’ expression mediators’ levels (pERK, p-p38, CD44, RUNX), enhanced secretion of lactate, several cytokines (IL8, IL6, CXCL1, CCL2, ICAM1), and proteins related to angiogenesis (GM-CSF, DPPIV, VEGFA, PIGF).,Observed changes in CAFs’ biology were mainly driven by highly aggressive melanoma cells (A375, WM9, Hs294T) compared to the less aggressive WM1341D cells and could promote melanoma invasion, as well as impact inflammation, angiogenesis, and acidification of the tumor niche.,Interestingly, different approaches to CAFs acquisition seem to complement each other showing interactions between studied cells.,Video Abstract,Video Abstract,The online version contains supplementary material available at 10.1186/s12964-022-00871-x.
Supplemental Digital Content is available in the text.,Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients’ survival.,This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences.,Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017).,Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses).,Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%).,A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences).,Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%).,The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes.,In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM.,It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.