A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma

Hardwick, Laura J.A.

doi:10.3390/vetsci8110286

Cited by 8 publications

(5 citation statements)

References 147 publications

(304 reference statements)

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“…Studying TAMs both as prognostic indicators and as therapeutic targets in canine melanocytic tumors seems to be a promising path to follow to increase the current knowledge of their role in these tumors. Indeed, melanocytic tumors, despite being common in dogs, have sometimes unpredictable behavior and no curative available therapies (23)(24)(25)(26)(27); therefore, studies investigating additional valid prognostic features and feasible targets for new therapeutic strategies are fundamental.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages in Canine Oral and Cutaneous Melanomas and Melanocytomas: Phenotypic and Prognostic Assessment

et al. 2022

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The tumor microenvironment is a complex system, where neoplastic cells interact with immune and stromal cells. Tumor-associated macrophages (TAMs) are considered among the most numerically and biologically noteworthy cellular components in tumors and the attention on this cellular population has been growing during the last decade, both for its prognostic role and as a potential future therapeutic target. Melanoma, particularly the oral form, despite being one of the most immunogenic tumors, bears a poor prognosis in dogs and humans, due to its highly aggressive biological behavior and limited therapeutic options. The aims of this study are to characterize and quantify TAMs (using CD163, CD204, Iba1, and MAC387) in canine melanocytic tumors and to evaluate the association of these markers with diagnosis, histologic prognostic features, presence of metastases, and outcome, and to provide preliminary data for possible future therapies targeting TAMs. Seventy-two melanocytic tumors (27 oral melanomas, 25 cutaneous melanomas, 14 cutaneous melanocytomas, and 6 oral melanocytomas) were retrospectively selected and submitted to immunohistochemistry and double immunofluorescence. Double immunolabeling revealed that most CD163+ and CD204+cells co-expressed Iba1, which labeled also dendritic cells. Iba1 was instead rarely co-expressed with MAC387. Nevertheless, the expression of macrophagic markers showed a mild to moderate association among the four markers, except for CD204 and MAC387. The number of CD163+, CD204+, and MAC387+ cells was significantly higher in oral melanomas compared to oral melanocytomas (p < 0.001; p < 0.05 and p < 0.01, respectively), whereas Iba1 was differentially expressed in cutaneous melanomas and melanocytomas (p < 0.05). Moreover, CD163, IBA1 and MAC387 expression was associated with nuclear atypia and mitotic count. The number of CD163+cells was associated with the presence of metastases and tumor-related death in oral melanocytic tumors (p < 0.05 and p = 0.001, respectively).

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Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages in Canine Oral and Cutaneous Melanomas and Melanocytomas: Phenotypic and Prognostic Assessment

et al. 2022

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“…However, some dog breeds are more affected, which suggests a genetic basis [1,65]. Even so, there is not total unanimity on which breeds are the most susceptible [68]; some researchers report an increased predisposition for Golden Retrievers, Cocker Spaniels, Miniature Poodles, Chow Chows, Gordon Setters, and Anatolian Sheep Dogs [56,69,70], while others do not find an overall breed predisposition [71]. Usually, affected dogs have very pigmented oral mucosa and skin; however, predisposing germline alleles have not been determined [51,72].…”

Section: Dog In a Perspective Of A Comparative Oncology Model For Hum...mentioning

confidence: 99%

The human and animals’ malignant melanoma: comparative tumor models and the role of microbiome in dogs and humans

2023

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Currently, the most progressively occurring incident cancer is melanoma. The mouse is the most popular model in human melanoma research given its various benefits as a laboratory animal. Nevertheless, unlike humans, mice do not develop melanoma spontaneously, so they need to be genetically manipulated. In opposition, there are several reports of other animals, ranging from wild to domesticated animals, that spontaneously develop melanoma and that have cancer pathways that are similar to those of humans. The influence of the gut microbiome on health and disease is being the aim of many recent studies. It has been proven that the microbiome is a determinant of the host's immune status and disease prevention. In human medicine, there is increasing evidence that changes in the microbiome influences malignant melanoma progression and response to therapy. There are several similarities between some animals and human melanoma, especially between canine and human oral malignant melanoma as well as between the gut microbiome of both species. However, microbiome studies are scarce in veterinary medicine, especially in the oncology field. Future studies need to address the relevance of gut and tissue microbiome for canine malignant melanoma development, which results will certainly benefit both species in the context of translational medicine. Melanoma Res 33: 87-103

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“… 2017 ; Turek et al. 2020 ; Hardwick 2021 ). In dogs, malignant melanoma has reported fatality rates of up to 75%, and death may often prove unpreventable even with 1-year treatment involving surgery and subsequent adjuvant therapy (Treggiari et al.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs

Hasan,

Rahman,

Husna

et al. 2024

Veterinary Quarterly

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Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.

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A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma

Cited by 8 publications

References 147 publications

Tumor-Associated Macrophages in Canine Oral and Cutaneous Melanomas and Melanocytomas: Phenotypic and Prognostic Assessment

Tumor-Associated Macrophages in Canine Oral and Cutaneous Melanomas and Melanocytomas: Phenotypic and Prognostic Assessment

The human and animals’ malignant melanoma: comparative tumor models and the role of microbiome in dogs and humans

Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs

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