Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets

Konstantakou, Eumorphia G.; Velentzas, Athanassios D.; Anagnostopoulos, Athanasios K.; Litou, Zoi I.; Konstandi, Ourania; Giannopoulou, Aikaterini F.; Anastasiadou, Ema; Voutsinas, Gerassimos E.; Tsangaris, George Th.; Stravopodis, Dimitrios J.

doi:10.1371/journal.pone.0171512

Cited by 21 publications

(62 citation statements)

References 150 publications

(192 reference statements)

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“…Cutaneous (skin) melanoma is one of the most aggressive and treatment-resistant human cancers [ 1 ]. Indeed, skin melanoma is characterized by a high tendency to metastasize since it is located in the basal layer of the epidermis, which is constituted by several blood and lymphatic vessels [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

et al. 2018

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Although most melanoma cases may be treated by surgical intervention upon early diagnosis, a significant portion of patients can still be refractory, presenting low survival rates within 5 years after the discovery of the illness. As a hallmark, melanomas are highly prone to evolve into metastatic sites. Moreover, melanoma tumors are highly resistant to most available drug therapies and their incidence have increased over the years, therefore leading to public health concerns about the development of novel therapies. Therefore, researches are getting deeper in unveiling the mechanisms by which melanoma initiation can be triggered and sustained. In this context, important progress has been achieved regarding the roles and the impact of cellular signaling pathways in melanoma. This knowledge has provided tools for the development of therapies based on the intervention of signal(s) promoted by these cascades. In this review, we summarize the importance of major signaling pathways (mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)-Akt, Wnt, nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), transforming growth factor β (TGF-β) and Notch) in skin homeostasis and melanoma progression. Available and developing melanoma therapies interfering with these signaling cascades are further discussed.

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Section: Introductionmentioning

confidence: 99%

Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

et al. 2018

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“…Although NDRG-1 was downregulated in melanoma compared to in nevus, we could not detect any difference between H-scores of primary and metastatic melanomas in tissue samples. It has been shown that NDRG-1 was downregulated in majority of cancers and acts as a metastasis suppressor protein in at least a group of human carcinomas (46,47,48). The importance of NDRG-1 in melanoma is not well known; strong NDRG-1 staining was seen in melanoma samples compared to in nevus.…”

Section: Discussionmentioning

confidence: 99%

Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF1-Beta and NDRG-1

Erçin¹,

Bozdoğan²,

Çavuşoğlu³

et al. 2019

Balkan Med J

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Background: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. Aims: To evaluate the difference of hypoxic gene expression signatures in primary melanoma cell lines and metastatic melanoma cell lines and to find the expression changes of hypoxia-related genes in primary melanoma cell lines at experimental hypoxic conditions Study Design: Cell study. Methods: The mRNA expression levels of hypoxia-related genes in primary melanoma cell lines and metastatic melanoma cell lines and at experimental hypoxic conditions in primary melanoma cell lines were evaluated by using real-time polymerase chain reaction. Depending on the experimental data, we focused on two genes/proteins, the hypoxia-inducible factor-1 beta and the N-myc downstream regulated gene-1. The expression levels of the two proteins were investigated by immunohistochemistry methods in 16 primary and metastatic melanomas, 10 intradermal nevi, and a commercial tissue array comprised of 208 cores including 192 primary and metastatic malignant melanomas. Results: The real-time polymerase chain reaction study showed that hypoxic gene expression signature was different between metastatic melanoma cell lines and primary melanoma cell lines. Hypoxic experimental conditions significantly affected the hypoxic gene expression signature. In immunohistochemical study, N-myc downstream regulated gene-1 expression was found to be lower in primary cutaneous melanoma compared to in intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of hypoxiainducible factor-1 beta was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between the two proteins studied in the study groups. Conclusion: Hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light on hypoxic processes in melanoma and unlock a Pandora's box for development of new therapeutic strategies.

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“…For example, (1) Osteopontin acts as a cytokine and is involved in type I immune responses. Osteopontin-dependent autocrine/paracrine signaling pathways are associated with metastatic melanoma [24], and the protein is involved in cell signaling that regulates tumor progression and metastasis [25]. (2) Carbonic anhydrase 1 participates in interleukin 12-mediated signaling pathways, while Carbonic anhydrase IX inhibitors can increase the sensitivity to chemotherapy and promote the apoptosis of melanoma cells [26].…”

Section: B16 Melanoma-bearing Micementioning

confidence: 99%

Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer

Pan

Liu

et al. 2020

Preprint

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Urine can accumulate changes and reflect early physiological and pathological changes of various diseases, such as tumors. Therefore, urine is an ideal source for identification of early biomarkers. In this study, melanoma and prostate cancer-bearing mouse models were established by subcutaneous injection of B16 and RM-1 cells, respectively. Urine samples were collected at four time points during tumor growth. Based on dataindependent acquisition (DIA) technology, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for quantitative analysis. Compared with those before the injection of B16 cells, 38 human homologous differential proteins were identified, and 18 proteins were reported to be related to melanoma. Before the tumor was visible, there were 4 differential proteins, and all were reported to be related to melanoma. Compared with that before the injection of RM-1 cells, a total of 14 human homologous differential proteins were identified, and 9 proteins were reported to be associated with prostate cancer. Before the tumor was palpable, 9 proteins showed significant differences. There were significant differences between the two tumor-bearing models. Through the above experiments and analysis, we found that the urine proteome can reflect the changes in the development and provide early biomarkers of the two tumors and provide clues for the early clinical diagnosis of these diseases.Skin melanoma is one of the most common cancers in the world [1]. Melanoma is produced by the malignant transformation of melanocytes. This disease can occur in any part of the skin and mucous membranes. Melanoma easily metastasizes and is highly invasive and malignant, leading to high mortality. The diagnosis of melanoma is based on a combination of clinical and pathological techniques, including physical examination, histopathological examination and imaging examination. However, due to its variable histological morphology, with little or even no visible pigment, it is difficult to diagnose patients in the early stage and distinguish this condition from benign nevus in the clinic, which makes its early diagnosis difficult [2]. Early treatment of melanoma is mainly surgery, and advanced treatment includes chemotherapy, targeted therapy and immunotherapy. Compared with chemotherapy alone, targeted therapy and immunotherapy have significantly improved the survival rate of patients with advanced melanoma, but these two therapies are usually limited by the drug resistance rate and are not universally applicable [3,4]. The absolute survival rate of patients is still very low [5]. The 5-year survival rates of skin melanoma at stage I to IV are 97% (stage IA), 84% (stage IB), 68%, 55%, and 17% [6]. Therefore, early diagnosis can lead to early treatment and improve the survival rate of patients.Prostate cancer is one of the most common malignant tumors in men. In Europe and America, the incidence rate is highest among those of all cancers in males. The mortality rate is second only to that of lung cancer, ranking second fo...

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Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets

Cited by 21 publications

References 150 publications

Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF1-Beta and NDRG-1

Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer

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