Could senescence phenotypes strike the balance to promote tumor dormancy?

Chiu, Fang-Yen; Kvadas, Raegan; Mheidly, Zeinab; Shahbandi, Ashkan; Jackson, James G.

doi:10.1007/s10555-023-10089-z

Cited by 4 publications

(3 citation statements)

References 216 publications

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“…In addition, both their velocity and persistence of migration were greater on senescent ECM, suggesting a coupling between these two traits (as has been proposed for mesenchymal migration) [ 38 , 39 ]. We define these cellular behaviors collectively as senescence-associated matrisomal phenotype (or SAMP, in semantic consonance with the well-known senescence associated secretory phenotype (SASP) [ 40 , 41 ]).…”

Section: Discussionmentioning

confidence: 99%

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

Thapa,

Banerjee,

Glimm

et al. 2023

Cell. Mol. Life Sci.

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Ovarian cancer is amongst the most morbid of gynecological malignancies due to its diagnosis at an advanced stage, a transcoelomic mode of metastasis, and rapid transition to chemotherapeutic resistance. Like all other malignancies, the progression of ovarian cancer may be interpreted as an emergent outcome of the conflict between metastasizing cancer cells and the natural defense mounted by microenvironmental barriers to such migration. Here, we asked whether senescence in coelom-lining mesothelia, brought about by drug exposure, affects their interaction with disseminated ovarian cancer cells. We observed that cancer cells adhered faster on senescent human and murine mesothelial monolayers than on non-senescent controls. Time-lapse epifluorescence microscopy showed that mesothelial cells were cleared by a host of cancer cells that surrounded the former, even under sub-confluent conditions. A multiscale computational model predicted that such colocalized mesothelial clearance under sub-confluence requires greater adhesion between cancer cells and senescent mesothelia. Consistent with the prediction, we observed that senescent mesothelia expressed an extracellular matrix with higher levels of fibronectin, laminins and hyaluronan than non-senescent controls. On senescent matrix, cancer cells adhered more efficiently, spread better, and moved faster and persistently, aiding the spread of cancer. Inhibition assays using RGD cyclopeptides suggested the adhesion was predominantly contributed by fibronectin and laminin. These findings led us to propose that the senescence-associated matrisomal phenotype of peritoneal barriers enhances the colonization of invading ovarian cancer cells contributing to the metastatic burden associated with the disease.

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Section: Discussionmentioning

confidence: 99%

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

Thapa,

Banerjee,

Glimm

et al. 2023

Cell. Mol. Life Sci.

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show abstract

“…It is also worth mentioning that while generating this response, it seems that ChatGPT based its answer on established research that describes the stability of the SAGA solely in the context of replicative senescence. Moreover, several opinion and review articles have recently argued quite convincingly that senescence could represent a form of tumor dormancy leading to cancer relapse, which have been overlooked by ChatGPT (Kirkland, 2023;Truskowski et al, 2023) (Chiu et al, 2023).…”

Section: Q2: Is Senescence Considered a Form Of Tumor Dormancy?mentioning

confidence: 99%

“…ChatGPT concludes by demonstrating that senescence and tumor dormancy occur through different cellular pathways, in response to different stimuli and for different purposes. However, several recent studies that investigated possible similarities between components of the senescence phenotype and hallmarks of dormancy suggest the existence of a link between the two processes (Chiu et al, 2023); more specifically, potential connections between hallmarks of senescence and angiogenic, immunogenic and cellular forms of tumor dormancy have been proposed. With respect to angiogenic dormancy, it is hypothesized that in a poorly vascularized, hypoxic area of a tumor, cells undergo both quiescence and senescence; in such cases, the SASP could contribute to the angiogenic switch required by tumor cells to escape the dormant state through the release of certain cytokines such as VEGF, IL-6, and FGF, which was observed in both in vitro and in vivo studies that investigated the role of the SASP in the formation of blood vessels in tumors (Mikuła-Pietrasik et al, 2016).…”

mentioning

confidence: 99%

A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research

Elshazly,

Shahin,

Al Shboul

et al. 2024

Mol Pharmacol

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The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

Thapa

Glimm

Saini

et al. 2023

Preprint

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Ovarian cancer is amongst the most morbid of gynecological malignancies due to its diagnosis at an advanced stage, a transcoelomic mode of metastasis, and rapid transition to chemotherapeutic resistance. Like all other malignancies, the progression of ovarian cancer may be interpreted as an emergent outcome of the conflict between metastasizing cancer cells and the natural defense mounted by microenvironmental barriers to such migration. Here, we asked whether senescence in coelom-lining mesothelia, brought about by drug exposure, affects their interaction with disseminated ovarian cancer cells. We observed that cancer cells adhered faster on, senescent human and murine mesothelial monolayers than non-senescent controls. Time-lapse epifluorescent microscopy showed that mesothelial cells were cleared by a host of cancer cells that surrounded the former, even under sub-confluent conditions. A multiscale computational model predicted that such colocalized mesothelial clearance under sub-confluence requires greater adhesion between cancer cells and senescent mesothelia. Consistent with the prediction, we observed that senescent mesothelia expressed extracellular matrix with higher levels of fibronectin, laminins and hyaluronan than non-senescent controls. On senescent matrix, cancer cells adhered more efficiently, spread better, and moved faster and persistently, aiding the spread of cancer. Inhibition assays using RGD cyclopeptides suggested the adhesion was predominantly contributed by fibronectin and laminin. These findings led us to propose that the senescence-associated matrisomal phenotype of peritoneal barriers enhances the colonization of invading ovarian cancer cells and their clearance contributing to the metastatic burden associated with the disease.

show abstract

Could senescence phenotypes strike the balance to promote tumor dormancy?

Cited by 4 publications

References 216 publications

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells

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