Role of the extracellular matrix proteins in the resistance of SP6.5 uveal melanoma cells toward cisplatin

Bérubé, Mélanie; Talbot, Mariève; Collin, Charles; Paquet-Bouchard, Carine; Germain, Lucie; Guérin, Sylvain L.; Petitclerc, Éric

doi:10.3892/ijo.26.2.405

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…15,16 Similar findings have also been reported for uveal melanoma cell lines adhering to laminin, collagen IV and fibronectin. 18 For cutaneous melanoma it is known that plating cells onto fibronectin prevents anoikis and that knockdown of tenascin-C can sensitise melanoma cells to doxorubicin treatment. 19,20 Although we have not considered it in the present study, it is also likely that other host cell types may also protect the cancer cells from drug-induced apoptosis.…”

Section: Fibroblasts Aid Resistance To Treatmentmentioning

confidence: 99%

Fibroblasts Contribute to Melanoma Tumor Growth and Drug Resistance

et al. 2011

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The role of tumour-stromal interactions in progression is generally well accepted but their role in initiation or treatment is less well understood. It is now generally agreed that rather than consisting solely of malignant cells, tumours consist of a complex dynamic mixture of cancer cells, host fibroblasts, endothelial cells, and immune cells that interact with each other and micro-environmental factors to drive tumour progression. We are particularly interested in stromal cells (for example fibroblasts) and stromal factors (for example fibronectin) as important players in tumour progression since they have also been implicated in drug resistance. Here we develop an integrated approach to understand the role of such stromal cells and factors in the growth and maintenance of tumours as well as their potential impact on treatment resistance, specifically in application to melanoma. Using a suite of experimental assays we show that melanoma cells can stimulate the recruitment of fibroblasts and activate them, resulting in melanoma cell growth by providing both structural (extra-cellular matrix proteins) and chemical support (growth factors). Motivated by these experimental results we construct a compartment model and use it to investigate the roles of both stromal activation and tumour aggressiveness in melanoma growth and progression. We utilise this model to investigate the role fibroblasts might play in melanoma treatment resistance and the clinically observed flare phenomena that is seen when a patient, who appears resistant to a targeted drug, is removed from that treatment. Our model makes the unexpected prediction that targeted therapies may actually hasten tumour progression once resistance has occurred. If confirmed experimentally, this provocative prediction may bring important new insights into how drug resistance could be managed clinically.

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Section: Fibroblasts Aid Resistance To Treatmentmentioning

confidence: 99%

Fibroblasts Contribute to Melanoma Tumor Growth and Drug Resistance

et al. 2011

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“…Зарубежными исследователями показано, что опухолевые клетки увеальной меланомы и в первичных, и в метастатических очагах окружены фиб ронектином, коллагеном IV типа, ламинином. Также в эксперименте in vitro М. Bérubé et al показано, что перечисленные белки формируют благоприятную микросреду для опухолевых клеток, делая их более устойчивыми в том числе к воздействию химиопрепарата (цисплатин) [21].…”

Section: Discussionunclassified

Morphological features of the distribution of extracellular matrix components MMP-9 and type IV collagen in metastatic choroidal melanoma

Shamanova¹,

Kazachkov²,

Панова³

2022

Clin. Exp. Morphology

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Introduction. Early diagnosis and prediction of distant metastases in choroidal melanoma patients based on morphological and IHC assessment of the components of the tumor microenvironment is a topical issue. The aim was to evaluate the IHC expression of MMP-9 and type IV collagen in metastatic choroidal melanoma. Materials and methods. We analyzed 43 cases of choroidal melanoma T2(a,b,c)-3N0M0-1 during 2013–2017. The patients were divided into two groups: group 1 included patients with primary choroidal melanoma without distant metastases (N=25) and group 2 included patients with primary choroidal melanoma with distant liver metastases (N=18). We performed an IHC assay of the surgical samples with MMP-9 (Poly) (MMP-9) and Collagen-IV (Clone CIV 22) (Col4) antibodies. Qualitative, semi-quantitative, and quantita-tive parameters were evaluated with digital pathology software. We developed a semi-quantitative method for estimating the intensity of IHC expression of these markers (in scores) in choroidal melanoma. Results. The study included 22 female and 21 male patients (51.2% and 48.8%, respectively), the average age being 60.5 years. The thickness of choroidal melanoma averaged 8.3 mm; the average diameter of the tumor was 12.3 mm. We detected strong MMP-9 expression in tumor cells and their microenvironment and remodeled collagen framework in tumors with pronounced tumor necrosis, thickness, and scleral involve-ment. A more pronounced expression of MMP-9 was associated with an increase in isolated type IV collagen fibers in the extracellular matrix (ECM) of the metastatic choroidal melanoma. Conclusion. During the growth and progression of choroidal melanoma, the components of the microenvi-ronment and tumor cells have a mutual effect with the disorganization of ECM components. Indicators of IHC expression (MMP-9, Col4) in a tumor should not be considered as a diagnostic marker of metastatic choroidal melanoma. However, they can be used in clinical practice when monitoring the course of the disease and in studying the mechanisms of remodeling of the tumor microenvironment. Keywords: choroidal melanoma, MMP-9, type IV collagen, metastasis

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“…Miyamoto H and colleagues have further found that the grade of differentiation of pancreatic tumor cells affects the interaction with different ECM macromolecules (fibronectin, collagen I, and collagen IV) as well as the matrix-driven sensitivity to chemotherapeutic drugs, including cisplatin (Miyamoto H et al, 2004). The presence of fibronectin, type IV collagen, and laminin have also been linked to cisplatin-resistance and local recurrence of uveal melanomas (Bérubé M et al, 2005). The authors observed that apoptosis was less frequent after cisplatin administration in the presence of ECM when compared with cells cultured on a non-permissive matrix (Bérubé M et al, 2005).…”

Section: The Tumor Stromamentioning

confidence: 99%

“…The presence of fibronectin, type IV collagen, and laminin have also been linked to cisplatin-resistance and local recurrence of uveal melanomas (Bérubé M et al, 2005). The authors observed that apoptosis was less frequent after cisplatin administration in the presence of ECM when compared with cells cultured on a non-permissive matrix (Bérubé M et al, 2005). Several studies also found that the overexpression of ECM-associated genes correlates with increased cisplatin resistance (Januchowski R et al, 2014;Sherman-Baust CA et al, 2011;Sherman-Baust CA et al, 2003).…”

Section: The Tumor Stromamentioning

confidence: 99%

Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

Ferreira

Peixoto

Neves

et al. 2016

Drug Resistance Updates

130

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Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omics models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics.

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Role of the extracellular matrix proteins in the resistance of SP6.5 uveal melanoma cells toward cisplatin

Cited by 9 publications

References 28 publications

Fibroblasts Contribute to Melanoma Tumor Growth and Drug Resistance

Fibroblasts Contribute to Melanoma Tumor Growth and Drug Resistance

Morphological features of the distribution of extracellular matrix components MMP-9 and type IV collagen in metastatic choroidal melanoma

Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

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