Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion

Ziani, Linda; Safta-Saadoun, Thouraya Ben; Gourbeix, Johanne; Cavalcanti, A.; Robert, Caroline; Favre, Gilles; Chouaı̈b, Salem; Thiery, Jérôme

doi:10.18632/oncotarget.15540

Cited by 105 publications

(86 citation statements)

References 61 publications

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“…S100 calcium binding protein A4 (S100A4), also known as fibroblast-specific protein 1 (FSP1), for example, is a marker that has been used in a number of publications in order to confirm the CAF phenotype of examined cells. [49][50][51] However, recent studies have raised some suspicion on the specificity of FSP1, as it has been observed to be less reliable for fibroblast identification from primary tumor samples than FAP. 25 It has also been confirmed to be expressed by metastatic prostate cancer-derived epithelial cell lines and tissues.…”

Section: Other Markersmentioning

confidence: 99%

In search of definitions: Cancer‐associated fibroblasts and their markers

Nurmik

Ullmann

Rodriguez

et al. 2019

Intl Journal of Cancer

497

428

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The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer‐associated fibroblasts (CAFs), a type of perpetually activated fibroblasts, have been implicated to have a strong tumor‐modulating effect and play a key role in areas such as drug resistance. Identification of CAFs has typically been carried based on the expression of various “CAF markers”, such as fibroblast activation protein alpha (FAP) and alpha smooth muscle actin (αSMA), which separates them from the larger pool of fibroblasts present in the body. However, as outlined in this Review, the expression of various commonly used fibroblast markers is extremely heterogeneous and varies strongly between different CAF subpopulations. As such, novel selection methods based on cellular function, as well as further characterizing research, are vital for the standardization of CAF identification in order to improve the cross‐applicability of different research studies in the field. The aim of this review is to give a thorough overview of the commonly used fibroblast markers in the field and their various strengths and, more importantly, their weaknesses, as well as to highlight potential future avenues for CAF identification and targeting.

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Section: Other Markersmentioning

confidence: 99%

In search of definitions: Cancer‐associated fibroblasts and their markers

Nurmik

Ullmann

Rodriguez

et al. 2019

Intl Journal of Cancer

497

428

View full text Add to dashboard Cite

show abstract

“…MICA/B work as the two ligands of NKG2D, express at the surface of tumour cells. Ziani et al showed that the increasing secretion of matrix metalloproteinases (MMPs) by CAFs in the melanoma tumour microenvironment could reduce the expression of MICA/B, therefore further decreasing the cytotoxic activity of NK cells to melanoma cancer cells which depended on NKG2D . Compared to the normal endometrial fibroblasts (NEFs), the expression of poliovirus receptor (PVR) was downregulated in CAFs .…”

Section: Crosstalk Between Cancer‐associated Fibroblasts and Immune Cmentioning

confidence: 99%

Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

Liu

Chen

et al. 2019

J Cellular Molecular Medi

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Multiple studies have shown that cancer‐associated fibroblasts (CAFs) play an important role in tumour progression, including carcinogenesis, invasion, metastasis and the chemoresistance of cancer cells. Immune cells, including macrophages, natural killer cells, dendritic cells and T cells, play a dual role in the tumour microenvironment. Although increasing research has focused on studying interactions between distinct cells in the tumour microenvironment, the complex relationships between CAFs and immune cells remain unclear and need further study. Here, we summarize our current understanding of crosstalk between CAFs and immune cells, which may help clarify their diagnostic and therapeutic value in tumour progression.

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“…Indeed, the cellular composition of regression includes tumour-associated macrophages and cancerassociated fibroblasts that are known to play a crucial role in tumour promotion. Conversely, tumourinfiltrating lymphocytes undoubtedly have antitumoural effects within the melanoma-derived microenvironment (Ziani et al 2017). Along these lines, regression may be considered a paradoxical one step forward to loco-regional and distant metastases.…”

Section: Main Clinical Types Of Primary Melanomamentioning

confidence: 99%

Clinical protein science in translational medicine targeting malignant melanoma

et al. 2019

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Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry-based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular

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Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion

Cited by 105 publications

References 61 publications

In search of definitions: Cancer‐associated fibroblasts and their markers

In search of definitions: Cancer‐associated fibroblasts and their markers

Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

Clinical protein science in translational medicine targeting malignant melanoma

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