Review
Cell Biology
Samuel Darkwah, Eun Jeong Park, Phyoe Kyawe Myint, Atsushi Ito, Michael G. Appiah, Gideon Obeng, Eiji Kawamoto, Motomu Shimaoka
Summary: EVs play a key role in intercellular communication, with muscle cell-derived EVs potentially modulating organ remodeling by carrying myokines and other substances, contributing to the establishment and modulation of pre-metastatic niches in vital sites for metastatic tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Patricia Gonzalez-Callejo, Petra Gener, Zamira Diaz-Riascos, Sefora Conti, Patricia Camara-Sanchez, Roger Riera, Sandra Mancilla, Miguel Garcia-Gabilondo, Vicente Peg, Diego Arango, Anna Rosell, Anna Labernadie, Xavier Trepat, Lorenzo Albertazzi, Jr Simo Schwartz, Joaquin Seras-Franzoso, Ibane Abasolo
Summary: Tumor-secreted extracellular vesicles play a crucial role in the establishment and growth of metastatic tumors. The diversity among these vesicles, particularly in triple-negative breast cancer, has not been fully explored. This study found that vesicles secreted by cancer stem cells and differentiated cancer cells have distinct effects on the tumor microenvironment, promoting different aspects of tumor growth and metastasis.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Elke Pach, Maike Kuemper, Julia E. Fromme, Jan Zamek, Fabian Metzen, Manuel Koch, Cornelia Mauch, Paola Zigrino
Summary: The deletion of MMP14 in dermal fibroblasts leads to the deposition of an extracellular matrix that inhibits melanoma growth, with collagen XIV identified as a key regulator in melanoma progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Min Kim, Changhu Lee, Jiyoung Park
Summary: Obesity is a global public health concern and a significant risk factor for metabolic diseases and various cancers. Fibro-inflammation and excessive extracellular matrix (ECM) production in adipose tissues play a crucial role in the pathogenesis of obesity. The ECM is a critical component of tissues, regulating cell survival, development, and tissue repair. ECM remodeling in adipose tissues affects the physical shape and biological function of adipose tissues, which in turn influences obesity-related cancer progression.
TRENDS IN CELL BIOLOGY
(2022)
Article
Engineering, Biomedical
Samuel Alkmin, Manish S. Patankar, Paul J. Campagnola
Summary: Ovarian cancer is the deadliest gynecological cancer due to poor screening and imaging tools as well as limited understanding of the tumor microenvironment. This study used multiphoton excited fabrication to create orthogonal models representing the collagen matrix morphology and stiffness of normal ovarian stroma and high grade serous ovarian cancers. The study found that fiber morphology and matrix stiffness play important roles in migration and cytoskeletal dynamics of normal and cancer cells, and cell-specific differences highlight the importance of presenting both morphology and stiffness cues.
ACTA BIOMATERIALIA
(2022)
Review
Biochemistry & Molecular Biology
Marina Marozzi, Arianna Parnigoni, Aide Negri, Manuela Viola, Davide Vigetti, Alberto Passi, Evgenia Karousou, Federica Rizzi
Summary: Cancer is a complex pathology characterized by uncontrolled cell proliferation and decreased apoptosis, often in an inflammatory environment. Changes in the extracellular matrix (ECM) and signaling pathways play crucial roles in tumor growth and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Laura Pulze, Nicolo Baranzini, Terenzio Congiu, Francesco Acquati, Annalisa Grimaldi
Summary: The leech is an important experimental animal model for studying the interaction between extracellular matrix and cells, and the role of ECM stiffness in development and growth. The study found that the structural organization of ECM and the amount of collagen vary greatly during leech development, which affects the migration of cells. The ability of cells to perceive and respond to changes in ECM composition and mechanics depends on the expression of Yes-Associated Protein 1 (YAP1).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Jian Gao, Xiaodong Zhang, Lei Jiang, Yan Li, Qianqian Zheng
Summary: Cancer progression involves key steps such as angiogenesis, and extracellular vesicles (EVs) released by tumor cells and other cells in the tumor microenvironment (TME) play a role in modulating and maintaining favorable conditions for tumor growth. EVs derived from endothelial cells (ECs) have important roles in tumor angiogenesis and can also activate tumor cells, facilitating extracellular matrix (ECM) remodeling and providing additional nutrients to tumor cells. Therefore, targeting EV communication between cancer cells and ECs could be an effective therapeutic approach for controlling cancer progression.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Immunology
Carmine Fedele, Shuai Li, Kai Wen Teng, Connor J. R. Foster, David Peng, Hao Ran, Paolo Mita, Mitchell J. Geer, Takamitsu Hattori, Akiko Koide, Yubao Wang, Kwan Ho Tang, Joshua Leinwand, Wei Wang, Brian Diskin, Jiehui Deng, Ting Chen, Igor Dolgalev, Ugur Ozerdem, George Miller, Shohei Koide, Kwok-Kin Wong, Benjamin G. Neel
Summary: The combination of SHP2 inhibitor and KRAS (G12C) inhibitor shows significant survival benefits in PDAC and NSCLC, inducing favorable changes in the tumor microenvironment by reducing myeloid suppressor cells, increasing CD8(+) T cells, and enhancing sensitivity to PD-1 blockade.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Qian Zhang, Zi-Yi An, Wen Jiang, Wei-Lin Jin, Xin-Yang He
Summary: “Collagen, a major component of the extracellular matrix (ECM), plays a crucial role in tumor progression within the tumor microenvironment (TME). Recent studies have shown that collagen deposition in the TME affects tumor progression and interacts with tumor cells in complex ways. These findings highlight the potential of collagen as a target for cancer therapy.”
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Tracy J. Berg, Alexander Pietras
Summary: Cancer cells often exploit stromal cells' functions to support tumor progression and resistance to treatment. Therapies targeting cancer cells also affect stromal cells, leading to various responses that may promote tumor progression and treatment resistance. This review focuses on the response of stromal cells to cancer therapy, particularly radiotherapy in glioblastoma. Understanding how stromal cells respond to therapy can provide insights into potential targets to enhance tumor response to existing treatments.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Ning Li, Xingqing Jia, Zhong Wang, Kaige Wang, Zumin Qu, Dong Chi, Zhubo Sun, Jian Jiang, Yougang Cui, Changmiao Wang
Summary: This study investigated the molecular characteristics and prognostic value of anoikis in pancreatic cancer and pancreatic neuroendocrine tumors. Anoikis-related genes were identified, and a prognostic model based on these genes was constructed and validated. The findings provide new insights into the significance of anoikis in these cancers and contribute to the advancement of precision oncology.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Simion C. Dinca, Daniel Greiner, Keren Weidenfeld, Laura Bond, Dalit Barkan, Cheryl L. Jorcyk
Summary: High co-expression of LOXL2 and OSM in IDC patients is associated with worse metastasis-free survival rates, while high levels of either individually are less impactful; LOXL2 expression is positively correlated with OSM/OSM receptor (OSMR) expression in IDC patients. Additionally, OSM-induced LOXL2 promotes an increase in ECM collagen I fiber crosslinking, leading to significant fiber alignment between cells and increased IDC cell invasion.
BREAST CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Huaqing Jing, Yingzi Ren, Yue Zhou, Min Xu, Sona Krizkova, Zbynek Heger, Qiang Lu, Siyu Wang, Xiaoyang Liang, Vojtech Adam, Nan Li
Summary: This study developed a new method for treating liver fibrosis by using nanoenzymes loaded with nilotinib to inhibit the activation of hepatic stellate cells and improve the microenvironment of liver fibrosis. It was found that these nanoenzymes effectively eliminated intrahepatic reactive oxygen species, alleviated the hypoxic microenvironment, and promoted collagen depletion. In mouse experiments, the nanoenzymes showed significant antifibrogenic effects without obvious long-term toxicity.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Reproductive Biology
Alexis Ouellette, Mala Mahendroo, Shanmugasundaram Nallasamy
Summary: This study aimed to investigate the remodeling and hormonal regulation of collagen and elastin fibers in the myometrium during pregnancy. The results showed that the gene and protein expressions of collagen and elastin were induced early in pregnancy and were differentially regulated by progesterone and estrogen. Additionally, imaging analysis revealed structural reorganization of collagen and elastin fibers during pregnancy.
BIOLOGY OF REPRODUCTION
(2022)
Article
Oncology
Arig Ibrahim-Hashim, Kimberly Luddy, Dominique Abrahams, Pedro Enriquez-Navas, Sultan Damgaci, Jiqiang Yao, Tingan Chen, Marilyn M. Bui, Robert J. Gillies, Cliona O'Farrelly, Christina L. Richards, Joel S. Brown, Robert A. Gatenby
Summary: The progression of cancer is influenced by evolutionary dynamics in both the tumor population and its host. Host species can evolve defense strategies, both immunologic and non-immunologic, against tumors over generations. However, cancer cell plasticity allows for effective counter strategies against host defenses.
BRITISH JOURNAL OF CANCER
(2021)
Correction
Genetics & Heredity
Erez Persi, Yuri I. Wolf, David Horn, Eytan Ruppin, Francesca Demichelis, Robert A. Gatenby, Robert J. Gillies, Eugene V. Koonin
NATURE REVIEWS GENETICS
(2021)
Review
Genetics & Heredity
Erez Persi, Yuri Wolf, David Horn, Eytan Ruppin, Francesca Demichelis, Robert A. Gatenby, Robert J. Gillies, Eugene Koonin
Summary: Intratumour heterogeneity and phenotypic plasticity enabled by various somatic aberrations, epigenetic and metabolic adaptations, play a crucial role in helping cancers resist treatment and survive under environmental stress. Understanding the interplay between genetic aberrations, the microenvironment, and epigenetic and metabolic cellular states is essential for early detection, prevention, and development of efficient therapeutic strategies for cancer.
NATURE REVIEWS GENETICS
(2021)
Article
Biophysics
Michal R. Tomaszewski, William Dominguez-Viqueira, Antonio Ortiz, Yu Shi, James R. Costello, Heiko Enderling, Stephen A. Rosenberg, Robert J. Gillies
Summary: Quantitative MRI measures reflecting tumor heterogeneity can provide a sensitive and robust biomarker of early XRT response. T2 IQR showed sensitivity for detection of XRT-induced tumor changes 72 hours after treatment, outperforming T2-weighted and diffusion-weighted MRI, with very good robustness. This method may in future be applied for personalization of radiotherapy through adaptive treatment paradigms.
NMR IN BIOMEDICINE
(2021)
Article
Multidisciplinary Sciences
Mehdi Damaghi, Jeffrey West, Mark Robertson-Tessi, Liping Xu, Meghan C. Ferrall-Fairbanks, Paul A. Stewart, Erez Persi, Brooke L. Fridley, Philipp M. Altrock, Robert A. Gatenby, Peter A. Sims, Alexander R. A. Anderson, Robert J. Gillies
Summary: The harsh microenvironment of ductal carcinoma in situ (DCIS) selects for a Warburg Effect (WE) phenotype through constitutive transcriptional reprogramming, with KLF4 potentially being an inducer of the WE phenotype. In vitro results were used to simulate DCIS phenotypic evolution using a mathematical model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Robert J. Gillies
Summary: Evidence suggests that cells at the tumor stromal interface express higher levels of proteins related to glycolytic metabolism, leading to acid production which is associated with increased metastatic potential. The molecular machinery responsible for acid export is being studied, and neutralizing the acidity may prevent local invasion and metastasis.
CLINICAL & EXPERIMENTAL METASTASIS
(2022)
Article
Cell Biology
Bryce Ordway, Robert J. Gillies, Mehdi Damaghi
Summary: Invasive cancers usually develop over a long period through somatic evolution, with heritable genetic and epigenetic changes leading to the emergence of aggressive clonal populations. The extracellular environment in solid tumors imposes various stresses on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis, a common stressor for cancer cells, affects lysosomal function over time, potentially leading to dysregulation that could be targeted for therapeutic interventions.
Article
Biology
Marisabel Rodriguez Messan, Mehdi Damaghi, Audrey Freischel, Yan Miao, Joel Brown, Robert Gillies, Dorothy Wallace
Summary: This study developed a new model of a consumer-resource system with mobility to explain competition between two breast cancer cell lines in different culture conditions. The research highlighted the crucial role of cell mobility in competition dynamics.
MATHEMATICAL BIOSCIENCES
(2021)
Article
Oncology
Wei Mu, Matthew B. Schabath, Robert J. Gillies
Summary: Radiomics provides an opportunity to uncover image-based biomarkers by converting and analyzing medical images into high-dimensional mineable data. However, the lack of a generally accepted analytic and reporting standard makes interstudy comparisons challenging. Comparing and combining results from multiple studies is essential for clinical application.
Article
Oncology
Audrey R. Freischel, Jamie K. Teer, Kimberly Luddy, Jessica Cunningham, Yael Artzy-Randrup, Tamir Epstein, Kenneth Y. Tsai, Anders Berglund, John L. Cleveland, Robert J. Gillies, Joel S. Brown, Robert A. Gatenby
Summary: Evolution plays a crucial role in the initiation and progression of cancer. In addition to driver mutations, natural selection conserves genes that are necessary for optimal cancer cell fitness. By studying subtypes of lung adenocarcinoma, we identified highly mutated and highly conserved genes, which have common utility in adapting to similar tissue environments and are critical for optimal fitness. Targeting tumor-specific conserved genes may represent an effective treatment strategy.
Article
Radiology, Nuclear Medicine & Medical Imaging
Michal R. Tomaszewski, Shuxuan Fan, Alberto Garcia, Jin Qi, Youngchul Kim, Robert A. Gatenby, Matthew B. Schabath, William D. Tap, Denise K. Reinke, Rikesh J. Makanji, Damon R. Reed, Robert J. Gillies
Summary: This study presents a novel clinical-radiomic approach for patient enrichment in clinical trials. The results show that by using an appropriate model for selective patient inclusion, the SARC021 trial could have achieved its primary survival objective for patients with metastatic soft-tissue sarcoma.
Proceedings Paper
Engineering, Biomedical
Rahul Paul, Sherzod Kariev, Dmitry Cherezov, Matthew B. Schabath, Robert J. Gillies, Lawrence O. Hall, Dmitry B. Goldgof
Summary: Radiomics is utilized for predicting the malignancy of lung nodules, and training CNN with texture images can improve classification accuracy, termed as Deep Radiomics.
MEDICAL IMAGING 2021: COMPUTER-AIDED DIAGNOSIS
(2021)
Article
Oncology
Ilke Tunali, Yan Tan, Jhanelle E. Gray, Evangelia Katsoulakis, Steven A. Eschrich, James Saller, Hugo J. W. L. Aerts, Theresa Boyle, Jin Qi, Albert Guvenis, Robert J. Gillies, Matthew B. Schabath
Summary: This study developed a concise model using radiomics and clinical data to predict survival outcomes in NSCLC patients undergoing immunotherapy. The high-risk group had significantly lower survival rates compared to the low-risk group in validation cohorts. The most informative radiomic feature, GLCM inverse difference, was associated with hypoxia-related carbonic anhydrase 9.
JNCI CANCER SPECTRUM
(2021)
Article
Medicine, Research & Experimental
Bruna Jardim-Perassi, Wei Mu, Suning Huang, Michal R. Tomaszewski, Jan Poleszczuk, Mahmoud A. Abdalah, Mikalai M. Budzevich, William Dominguez-Viqueira, Damon R. Reed, Marilyn M. Bui, Joseph O. Johnson, Gary Martinez, Robert J. Gillies
Summary: The study successfully identified hypoxic habitats in tumors using deep learning models and multiparametric MRI, and monitored the response to TH-302 in sarcoma mouse models. The results showed that this approach can accurately predict hypoxic status and treatment response, helping to prevent the development of drug resistance.
Article
Oncology
Maximilian A. R. Strobl, Jeffrey West, Yannick Viossat, Mehdi Damaghi, Mark Robertson-Tessi, Joel S. Brown, Robert A. Gatenby, Philip K. Maini, Alexander R. A. Anderson
Summary: The key factor in determining the effectiveness of adaptive therapy is the cost of resistance in cancer cells. Tumors close to their carrying capacity may not require a cost, while tumors far from capacity may need a cost to see meaningful gains. Cell turnover plays a crucial role in modulating the impact of a resistance cost, highlighting its importance in resistance management through adaptive therapy.