scholarly journals Paracrine behaviors arbitrate parasite-like interactions between tumor subclones

2020 ◽  
Author(s):  
Robert J. Noble ◽  
Viola Walther ◽  
Christian Roumestand ◽  
Urszula Hibner ◽  
Michael E. Hochberg ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Mammary Cancer ◽  
Tumour Growth ◽  
Growth Dynamics ◽  
Treatment Resistance ◽  
Cellular Interactions ◽  
Mammary Cancer Cell ◽  
Tumour Growth Rate

AbstractExplaining the emergence and maintenance of intratumour heterogeneity is an important question in cancer biology. Tumour cells can generate considerable subclonal diversity, which influences tumour growth rate, treatment resistance and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactions in vitro. Surprisingly, we found that compared to monoculture, growth of the ‘winner’ was enhanced by the presence of the ‘loser’ cell line, whereas growth of the latter was reduced. Our assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively ‘farming’ the loser. Our findings add a new level of complexity to the mechanisms underlying the subclonal growth dynamics and suggest that in vivo tumour interactions could be more diverse than previously thought..

scholarly journals Paracrine Behaviors Arbitrate Parasite-Like Interactions Between Tumor Subclones

2021 ◽  
Vol 9 ◽  
Author(s):  
Robert J. Noble ◽  
Viola Walther ◽  
Christian Roumestand ◽  
Michael E. Hochberg ◽  
Urszula Hibner ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Cancer Biology ◽  
Mammary Cancer ◽  
Growth Dynamics ◽  
Treatment Resistance ◽  
Tumor Growth Rate ◽  
Intratumor Heterogeneity ◽  
Cellular Interactions ◽  
Mammary Cancer Cell

Explaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactions in vitro. Surprisingly, we found that, compared to monoculture, growth of the “winner” was enhanced by the presence of the “loser” cell line, whereas growth of the latter was reduced. Mathematical modeling and laboratory assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively “farming” the loser. Our findings add a new level of complexity to the mechanisms underlying subclonal growth dynamics.

scholarly journals Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities

2021 ◽  
Author(s):  
Richard S. Metcalfe ◽  
Rachael Kemp ◽  
Shane M. Heffernan ◽  
Rachel Churm ◽  
Yung-Chih Chen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cancer Cell ◽  
Cancer Biology ◽  
Tumour Growth ◽  
Exercise Physiology ◽  
Future Research ◽  
Cell Behaviour ◽  
Rna Molecules

AbstractRegular physical activity reduces the risk of several site-specific cancers in humans and suppresses tumour growth in animal models. The mechanisms through which exercise reduces tumour growth remain incompletely understood, but an intriguing and accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. This suggests that exercise can impact tumour biology through direct changes in circulating proteins, RNA molecules and metabolites. Here, we provide a comprehensive narrative overview of what is known about the effects of exercise-conditioned sera on in vitro cancer cell behaviour. In doing so, we consider the key limitations of the current body of literature, both from the perspective of exercise physiology and cancer biology, and we discuss the potential in vivo physiological relevance of these findings. We propose key opportunities for future research in an area that has the potential to identify key anti-oncogenic protein targets and optimise physical activity recommendations for cancer prevention, treatment and survivorship.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence

2019 ◽  
Vol 25 (28) ◽  
pp. 3020-3027 ◽  
Author(s):  
Mir W. Sekandarzad ◽  
Chris Doornebal ◽  
Markus W. Hollmann
Keyword(s):  
Pain Management ◽  
Cancer Biology ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Standard Of Care ◽  
Cancer Surgery ◽  
Perioperative Pain Management ◽  
Tumor Growth And Metastasis

: Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. : The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. : This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to the immune-modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that yielded neutral or even anti-carcinogenic effects are presented here. : Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.

scholarly journals Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Yu Tian ◽  
Bo Tang ◽  
Chengye Wang ◽  
Yan Wang ◽  
Jiakai Mao ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Sirtuin 1 ◽  
Mesenchymal Transition ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Paired Tumour

AbstractOncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development.

scholarly journals Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis

2021 ◽  
Vol 16 (1) ◽  
pp. 523-536
Author(s):  
Minghao Li ◽  
Jianbin Zhuang ◽  
Di Kang ◽  
Yuzhuo Chen ◽  
Weiliang Song
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Spindle Pole ◽  
Circular Rnas ◽  
Cell Progression ◽  
Crc Management ◽  
Common Malignancy

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

scholarly journals The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Luisa Statello ◽  
Mohamad M Ali ◽  
Silke Reischl ◽  
Sagar Mahale ◽  
Subazini Thankaswamy Kosalai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cancer Biology ◽  
Topoisomerase I ◽  
Cell Cycle Checkpoints ◽  
Topoisomerase 1 ◽  
Damage Response ◽  
Promote Cell Survival

Abstract Despite the rapid improvements in unveiling the importance of lncRNAs in all aspects of cancer biology, there is still a void in mechanistic understanding of their role in the DNA damage response. Here we explored the potential role of the oncogenic lncRNA SCAT7 (ELF3-AS1) in the maintenance of genome integrity. We show that SCAT7 is upregulated in response to DNA-damaging drugs like cisplatin and camptothecin, where SCAT7 expression is required to promote cell survival. SCAT7 silencing leads to decreased proliferation of cisplatin-resistant cells in vitro and in vivo through interfering with cell cycle checkpoints and DNA repair molecular pathways. SCAT7 regulates ATR signaling, promoting homologous recombination. Importantly, SCAT7 also takes part in proteasome-mediated topoisomerase I (TOP1) degradation, and its depletion causes an accumulation of TOP1–cc structures responsible for the high levels of intrinsic DNA damage. Thus, our data demonstrate that SCAT7 is an important constituent of the DNA damage response pathway and serves as a potential therapeutic target for hard-to-treat drug resistant cancers.

scholarly journals P2X7 Receptor Promotes Mouse Mammary Cancer Cell Invasiveness and Tumour Progression, and Is a Target for Anticancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2342 ◽  
Author(s):  
Lucie Brisson ◽  
Stéphanie Chadet ◽  
Osbaldo Lopez-Charcas ◽  
Bilel Jelassi ◽  
David Ternant ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
P2x7 Receptor ◽  
Mammary Cancer ◽  
Tumour Progression ◽  
Mammary Cancer Cell ◽  
Cell Invasiveness ◽  
Cancer Cell Invasiveness

The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment.

scholarly journals Automated analysis of filopodial length and spatially resolved protein concentration via adaptive shape tracking

2016 ◽  
Vol 27 (22) ◽  
pp. 3616-3626 ◽  
Author(s):  
Tanumoy Saha ◽  
Isabel Rathmann ◽  
Abhiyan Viplav ◽  
Sadhana Panzade ◽  
Isabell Begemann ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Growth Dynamics ◽  
Automated Analysis ◽  
Cell Types ◽  
Control Mechanisms ◽  
Spatially Resolved ◽  
Novel Approach ◽  
Associated Proteins

Filopodia are dynamic, actin-rich structures that transiently form on a variety of cell types. To understand the underlying control mechanisms requires precise monitoring of localization and concentration of individual regulatory and structural proteins as filopodia elongate and subsequently retract. Although several methods exist that analyze changes in filopodial shape, a software solution to reliably correlate growth dynamics with spatially resolved protein concentration along the filopodium independent of bending, lateral shift, or tilting is missing. Here we introduce a novel approach based on the convex-hull algorithm for parallel analysis of growth dynamics and relative spatiotemporal protein concentration along flexible filopodial protrusions. Detailed in silico tests using various geometries confirm that our technique accurately tracks growth dynamics and relative protein concentration along the filopodial length for a broad range of signal distributions. To validate our technique in living cells, we measure filopodial dynamics and quantify spatiotemporal localization of filopodia-associated proteins during the filopodial extension–retraction cycle in a variety of cell types in vitro and in vivo. Together these results show that the technique is suitable for simultaneous analysis of growth dynamics and spatiotemporal protein enrichment along filopodia. To allow readily application by other laboratories, we share source code and instructions for software handling.

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