Heat shock protein expression in canine osteosarcoma

Romanucci, Mariarita; D'Amato, G.; Malatesta, Daniela; Bongiovanni, Laura; Palmieri, Chiara; Ciccarelli, Andrea; Buracco, Paolo; Morello, Emanuela; Maniscalco, Lorella; Maria, Raffaella De; Martano, Marina; Salda, Leonardo Della

doi:10.1007/s12192-011-0294-2

Cited by 13 publications

(8 citation statements)

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“…42 We have previously showed that Hsp90 is over-expressed in canine OSA tissues, suggesting a role in tumour progression and that in vitro treatment with 17-AAG induced autophagy and apoptosis in D17 cell line. 21,25 As showed in these results, 17-AAG induced a significant decrease of VM features in a time-dependent manner in D17 cell line, confirming the relevant biologic effect mediated by overcitated molecule on this canine OSA cell line.…”

Section: Discussionsupporting

confidence: 79%

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Establishment of three‐dimensional canine osteosarcoma cell lines showing vasculogenic mimicry and evaluation of biological properties after treatment with 17‐AAG

Massimini

Maria

Malatesta

et al. 2019

Vet Comparative Oncology

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Vasculogenic mimicry (VM) is an alternative type of blood perfusion characterized by formation of non‐endothelial cell‐lined microcirculatory channels and is responsible for aggressive tumour biology and increased tumour‐related mortality. VM‐correlated genes are associated with vascular endothelial grown factor receptor 1 (VEGFR1), and hypoxia‐related (hypoxia inducible factor 1 α—HIF1α) signalling pathways, whose molecules are client proteins of Hsp90 (heat shock protein 90) and are potential therapeutic targets. This pilot study was aimed to investigate vasculogenic mimicry in a three‐dimensional (3D) cell culture system of two aggressive canine osteosarcoma (OSA) cell lines (D22 and D17), and to evaluate the response of these cells to 17‐AAG (17‐N‐allylamino‐17‐demethoxygeldanamycin) treatment in relation to tubular‐like structure formation in vitro. Only D17 cell line formed hollow matrix channels in long‐term 3D cultures and assumed endothelial morphology, with cells expressing both Hsp90 and VEGFR1, but lacking expression of endothelial marker CD31. 17‐AAG treatment inhibited migration of D17 OSA cells, also decreasing VM markers in vitro and inducing a reduction of HIF1α transcript and protein in this cell line. Taken together, these preliminary data indicate that the biological effects of 17‐AAG on D17 3D culture and on HIF1α regulation can provide interesting information to translate these findings from the basic research to clinical approach for the treatment of canine OSA as a model in comparative oncology.

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Section: Discussionsupporting

confidence: 79%

“…Negative and positive controls were performed in all instances by omitting the primary Abs, or by using canine hemangiosarcoma (for CD31 and VEGFR1) or OSA (for Hsp90) tissue sections, respectively. The Abs used in all experimental sections were previously validated for canine tissues …”

Section: Methodsmentioning

confidence: 99%

Establishment of three‐dimensional canine osteosarcoma cell lines showing vasculogenic mimicry and evaluation of biological properties after treatment with 17‐AAG

Massimini

Maria

Malatesta

et al. 2019

Vet Comparative Oncology

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“…Numerous histological and biological features have been shown to be shared by canine and human OSA to date [3-8], even if further studies are warranted to define more precisely similarities and differences of OSA in the two species, so as to really consider the dog as a valuable spontaneous tumour model for human OSA. Even if several pathways have been investigated in canine OSA so far, few molecules have been identified as prognostic tools or potential therapeutic targets [5,9-18]. Leading on from this, there is still the need to investigate molecular pathways with specific influence over canine OSA progression to facilitate earlier prognosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, β-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

et al. 2012

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BackgroundOsteosarcoma (OSA) represents the most common canine primary bone tumour. Despite several pathways have been investigated so far, few molecules have been identified as prognostic tools or potential therapeutic targets, and there is still the need to find out molecular pathways with specific influence over OSA progression to facilitate earlier prognosis and treatment.Aims of the present study were to evaluate the immunohistochemical pattern and levels of expression of a panel of molecules (survivin, β-catenin, caspase 3 -inactive and active forms- and p53) involved in cell cycle and apoptosis regulation in canine OSA samples, known to be of interest in the study also of human OSA, and to detect specific relations among them and with histological tumour grade, disease free interval (DFI) and overall survival (OS).ResultsNuclear β-catenin immunostaining was detected in normal osteoblasts adjacent to the tumour, and in 47% of the cases. Cytoplasmic and/or membranous immunostaining were also observed. Nuclear survivin and p53 positive cells were found in all cases. Moderate/high cytoplasmic β-catenin expression (≥10% positive cells) was significantly associated with the development of metastasis (P = 0.014); moderate/high nuclear p53 expression (≥10% positive cells) was significantly associated with moderate/high histological grade (P = 0.017) and shorter OS (P = 0.049). Moderate/high nuclear survivin expression (≥15% positive cells) showed a tendency toward a longer OS (P = 0,088).ConclusionsThe present results confirmed p53 as negative prognostic marker, while suggested survivin as a potential positive prognostic indicator, rather than indicative of a poor prognosis. The detection of nuclear β-catenin immunostaining in normal osteoblasts and the absent/low expression in most of the OSAs, suggested that this pathway could not play a major role in oncogenic transformation of canine osteoblasts. Further studies are needed to confirm these hypotheses.

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“…15 In canine osteosarcoma (OSA), Hsp90 is expressed both in the primary tumor and in lymphatic emboli without a significant association with the histologic type. 27…”

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17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines

et al. 2016

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Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 μM, 1 μM) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy, and mitophagy were assessed by transmission electron microscopy, flow cytometry, and immunofluorescence. A simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

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Heat shock protein expression in canine osteosarcoma

Cited by 13 publications

References 30 publications

Establishment of three‐dimensional canine osteosarcoma cell lines showing vasculogenic mimicry and evaluation of biological properties after treatment with 17‐AAG

Establishment of three‐dimensional canine osteosarcoma cell lines showing vasculogenic mimicry and evaluation of biological properties after treatment with 17‐AAG

Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, β-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines

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