Immunohistochemical detection of senescence markers in human sarcomas

Giatromanolaki, Alexandra; Kouroupi, Maria; Balaska, Konstantina; Koukourakis, Michael I.

doi:10.1016/j.prp.2019.152800

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…The escape‐from‐senescence phenomenon could also be a mechanism contributing to this outcome (see the next section). Ever since GL13 discovery, the spectrum of pathological entities has been expanded to include benign, preneoplastic, and neoplastic lesions, while senescent cells have also been recognised in various experimental and ageing contexts (Table 2) [37,106,107,110–137]. In particular, in clinical settings, skin pathologies (nevi, seborrheic, and actinic keratoses), lung, pancreatic, urothelial and laryngeal precancerous lesions, various types of carcinomas following treatment, sarcomas, haematological malignancies (Langerhans histiocytosis), and a variety of tissues from aged organs were included (Table 2).…”

Section: Detecting Senescence Escape: a Challenging Taskmentioning

confidence: 99%

Escape from senescence: molecular basis and therapeutic ramifications

Evangelou

Belogiannis

Papaspyropoulos

et al. 2023

The Journal of Pathology

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Cellular senescence constitutes a stress response mechanism in reaction to a plethora of stimuli. Senescent cells exhibit cell‐cycle arrest and altered function. While cell‐cycle withdrawal has been perceived as permanent, recent evidence in cancer research introduced the so‐called escape‐from‐senescence concept. In particular, under certain conditions, senescent cells may resume proliferation, acquiring highly aggressive features. As such, they have been associated with tumour relapse, rendering senescence less effective in inhibiting cancer progression. Thus, conventional cancer treatments, incapable of eliminating senescence, may benefit if revisited to include senolytic agents. To this end, it is anticipated that the assessment of the senescence burden in everyday clinical material by pathologists will play a crucial role in the near future, laying the foundation for more personalised approaches. Here, we provide an overview of the investigations that introduced the escape‐from‐senescence phenomenon, the identified mechanisms, as well as the major implications for pathology and therapy. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Detecting Senescence Escape: a Challenging Taskmentioning

confidence: 99%

Escape from senescence: molecular basis and therapeutic ramifications

Evangelou

Belogiannis

Papaspyropoulos

et al. 2023

The Journal of Pathology

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“…Given that no single universal senescence marker has been identified to date [ 11 , 24 , 195 ] detection of senescent cells in tissues is conventionally attained by using a battery of immunohistochemical approaches [ 196 ] to probe for the presence of molecular biomarkers involved in signalling pathways specific for tumour suppression (e.g., p53 and RB) or cell‐cycle arrest (e.g., p16 INKA and p21 WAF1/CIP1 ), senescence‐associated epigenetic changes (e.g., SAHFs and H3K9me3), lack of proliferative capacity assessed by monitoring the incorporation of nucleoside analogues [e.g., 5‐bromo‐2′‐deoxyuridine (BrdU) or 5‐ethynyl‐2′‐deoxyuridine (EdU)] into newly synthesised DNA, together with the detection of elevated SAβG activity [ 197 ]. In addition to their intrinsic specificity issues, the conventional methods also require fresh or deep‐frozen tissues, which further restrict their use in in vivo settings for real‐time senescence detection.…”

Section: Approaches For the Detection Of Senescence In Cancermentioning

confidence: 99%

Cellular senescence in cancer: from mechanisms to detection

et al. 2020

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Senescence refers to a cellular state featuring a stable cell-cycle arrest triggered in response to stress. This response also involves other distinct morphological and intracellular changes including alterations in gene expression and epigenetic modifications, elevated macromolecular damage, metabolism deregulation and a complex pro-inflammatory secretory phenotype. The initial demonstration of oncogene-induced senescence in vitro established senescence as an important tumour-suppressive mechanism, in addition to apoptosis. Senescence not only halts the proliferation of premalignant cells but also facilitates the clearance of affected cells through immunosurveillance. Failure to clear senescent cells owing to deficient immunosurveillance may, however, lead to a state of chronic inflammation that nurtures a pro-tumorigenic microenvironment favouring cancer initiation, migration and metastasis. In addition, senescence is a response to post-therapy genotoxic stress. Therefore, tracking the emergence of senescent cells becomes pivotal to detect potential pro-tumorigenic events. Current protocols for the in vivo detection of senescence require the analysis of fixed or deep-frozen tissues, despite a significant clinical need for real-time Abbreviations 5-FU, 5-fluorouracil; AAH, atypical adenomatous hyperplasia, AIS adenocarcinoma in situ; ATM, ataxia-telangiectasia mutated; ATR, ATMand Rad3-related; B2M, b2-microglobulin; BAX, BCL2-associated protein X; BCL-2, B-cell lymphoma 2; BrdU, 5-bromo-2 0-deoxyuridine; C/ EBPb, CCAAT/enhancer-binding protein beta; CCF, cytoplasmic chromatin fragment; CDK, cyclin-dependent kinase; cfDNA, cell-free DNA; cGAS-STING, cyclic GMP-AMP synthase linked to stimulator of interferon genes; CHK, checkpoint kinase; CIS

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“…SenTraGor™ (STG) (Cat no: AR8850040, Arriani pharmaceuticals, Attika, Greece) reagent was used to stain lipofuscin granules in cancer cells. Details of the mixed histochemical/immunohistochemical method applied have been previously reported by our group (13). The percentage of tumor cells expressing STG in the cytoplasm was assessed in all-optical ×200 fields.…”

Section: Ethics the Hospital Scientific Committee And The Ethics Researchmentioning

confidence: 99%

“…This is based on the synthesis of a hapten-linked SBB analog (12). This method allows the assessment of senescence in paraffin-embedded tissue material (13).…”

mentioning

confidence: 99%

A Novel Lipofuscin-detecting Marker of Senescence Relates With Hypoxia, Dysregulated Autophagy and With Poor Prognosis in Non-small-cell-lung Cancer

Giatromanolaki

Kouroupi

Balaska

et al. 2020

In Vivo

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Background/Aim: The role of senescence in defining tumor aggressiveness at a clinical level remains obscure. A novel mixed histochemical/immunohistochemical method (SenTraGor™, STG) detecting lipofuscin accumulation allows the assessment of senescent cells in paraffin-embedded tissue material. Materials and Methods: STG expression was quantified in 98 surgically resected primary non-small-cell-lung carcinomas (NSCLC). Data were analyzed in parallel with other immunohistochemical markers related to hypoxia and autophagy. Results: Strong STG staining was noted in 36/98 cases (36.7%). High STG expression was significantly associated with high HIF1α expression and high expression of glucose (GLUT1) and monocarboxylate (MCT2) transporters, pointing to a link between senescence, hypoxia and glycolysis. High STG expression was also linked with high cytoplasmic accumulation of MAP1-LC3B, TFEB and LAMP2a, suggestive of a blockage of autophagy flux in tumors with intense senescence. Survival analysis showed a direct association with poor survival, independently of stage. Conclusion: SenTraGor™ provides a reliable methodology to detect lipofuscin accumulation in cancer cells in paraffinembedded tissues, opening a new field for translational studies focused on senescence.

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Immunohistochemical detection of senescence markers in human sarcomas

Cited by 12 publications

References 23 publications

Escape from senescence: molecular basis and therapeutic ramifications

Escape from senescence: molecular basis and therapeutic ramifications

Cellular senescence in cancer: from mechanisms to detection

A Novel Lipofuscin-detecting Marker of Senescence Relates With Hypoxia, Dysregulated Autophagy and With Poor Prognosis in Non-small-cell-lung Cancer

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