Sparc and melanoma

Secreted protein acidic and rich in cysteine (SPARC), a conserved secreted glycoprotein, plays crucial roles in regulating various biological processes. SPARC is highly expressed and has profound implications in several cancer types, including melanoma. Understanding the mechanisms that govern SPARC expression in cancers has the potential to lead to improved cancer diagnosis, prognosis, treatment strategies, and patient outcomes. Here, we demonstrate that histone deacetylase 10 (HDAC10) is a key regulator of SPARC expression in melanoma cells...

UNLABELLED: Secreted Protein Acidic and Rich in Cysteine (SPARC), a highly conserved secreted glycoprotein, is crucial for various bioprocesses. Here we demonstrate that histone deacetylase 10 (HDAC10) is a key regulator of SPARC expression. HDAC10 depletion or inhibition upregulates, while overexpression of HDAC10 downregulates, SPARC expression. Mechanistically, HDAC10 coordinates with histone acetyltransferase p300 to modulate the acetylation state of histone H3 lysine 27 (H3K27ac) at SPARC regulatory elements and the recruitment of bromodomain-containing protein 4 (BRD4) to these regions, thereby tuning SPARC transcription...

PURPOSE: Emergent cancer cells likely secrete factors that inhibit anti-tumor immunity. To identify such factors, we applied a functional assay with proteomics to an immunotherapy resistant syngeneic mouse melanoma model. Four secreted factors were identified that potentially mediate immunosuppression and could become targets for novel immunotherapies. We tested for consistent clinical correlates in existing human data and verified in vivo whether knocking out tumor cell production of these factors improved immune-mediated control of tumor growth...

BACKGROUND: The accumulation of reactive oxygen species (ROS) in tumor microenvironment (TME) is an important player for tumorigenesis and progression. We aimed to explore the outcomes of ROS on tumor vessels and the potential regulated mechanisms. METHODS: Exogenous H2 O2 was adopted to simulate the ROS setting. Immunofluorescence staining and ultrasonography were used to assess the vascular endothelial coverage and perfusions in the tumors inoculated with Lewis lung cancer (LLC) and melanoma (B16F10) cells of C57BL/6 mice, respectively...

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples...

The mechanism of melanoma metastasis is poorly understood, especially at the single-cell level. To understand the evolution from primary melanoma to metastasis, we investigated single-cell transcriptome profiles of parental B16 melanoma cells (B16F0) and its highly metastatic subclone (B16F10). Genomic alterations between cells were also analyzed by whole-exome sequencing. We identified 274 differentially expressed genes (DEGs) in B16F10, including upregulated genes related to metastasis, Lgals3, Sparc, Met, and Tmsb4x, and downregulated Mitf pathway genes, Ptgds, Cyb5a, and Cd63...

Primary cutaneous melanoma generally arises in the epidermis, followed by invasion into the dermis. Although infrequent, invasive melanoma cells can, alternatively, migrate to the intraepidermal area and form epidermotropic melanoma metastasis (EMM). In this study, we focused on this unique manner of metastasis. To identify the key molecules which affect EMM, gene expression in EMM was compared with that in common skin metastasis (CSM). Polymerase chain reaction (PCR) analysis was performed for genes affecting the extracellular matrix, cellular adhesion, and tumor metastasis on three EMM and three CSM samples as an initial screening...

Metastasis of melanoma to the distant organs is a multistep process in which the tumor microenvironment (TME) may play an important role. However, the relationship between metastatic progression and TME is intricate. In the present study, using melanoma derivative cell lines OL (oligometastatic) and POL (polymetastatic) that differ in their metastatic colonization capability, we have elucidated a new mechanism involving "SEC23A-PF4-MAPK/ERK axis" in which PF4 transported by COPII hinders metastasis through inhibition of MAPK/ERK signaling pathway...

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells...

Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor-host crosstalk, priming the tumor microenvironment to better support tumor growth and metastasis. We have utilized mice over-expressing (Hpa-tg) heparanase to reveal the role of host heparanase in tumor initiation, growth and metastasis. While in wild type mice tumor development in response to DMBA carcinogenesis was restricted to the mammary gland, Hpa-tg mice developed tumors also in their lungs and liver, associating with reduced survival of the tumor-bearing mice...

Migration and metastasis of tumor cells greatly contributes to the failure of cancer treatment. Recently, the extracellular protein secreted protein acidic and rich in cysteine (SPARC) has been reported closely related to tumorigenesis. Some articles have suggested that SPARC promoted metastasis in several highly metastatic tumors. However, there are also some studies shown that SPARC acted as an antitumor factor. SPARC-induced epithelial-to-mesenchymal transition (EMT) in melanoma cells and promoted EMT in hepatocellular carcinoma...

BACKGROUND: Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity. DESIGN: Fifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC)...

Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid carcinoma and meningioma. Although NPIs have been described in melanocytic lesions, there is no systematic analysis of potential relationship between NPIs and other clinicopathological characteristics of melanoma. We examined the presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed statistical associations with important clinicopathological parameters and tissue immunoreactivity for selected proteins involved in epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi apparatus (GOLPH3, GP73)...

Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model...

BACKGROUND: The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients...

Nanoparticles are used to deliver anticancer drugs to solid tumors. However, clinical development of nanoparticles is challenging because of their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles...

AIM: To investigate secreted protein acidic and rich in cystein (SPARC) and neural cadherin (NCAD), which are associated with epithelial-mesenchymal transition in primary skin melanoma and nodal metastases and their prognostic impact in melanoma patients. METHODS: Expression of proteins was assessed by immunochemistry in archival paraffin samples from 103 primary melanoma tumors and 16 nodal metastases. RESULTS: Increased expression of SPARC and NCAD in primary skin melanoma was associated with decreased overall survival, adverse clinicopathological features and particularly with microsatellitosis (SPARC) and ulceration (NCAD)...

Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of "unwanted-self" components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma. Despite its tumor-promoting role in mouse models of melanoma and lymphoma the expression and functional role of stabilin-1 in breast cancer was unknown...

BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS)...

Cell transition to a more aggressive mesenchymal-like phenotype is a hallmark of cancer progression that involves different steps and requires tightly regulated cell plasticity. SPARC (Secreted Protein Acidic and Rich in Cysteine) is a matricellular protein that promotes this transition in various malignant cell types, including melanoma cells. We found that suppression of SPARC expression in human melanoma cells compromised cell migration, adhesion, cytoskeleton structure, and cell size. These changes involved the Akt/mTOR pathway...