Article
Multidisciplinary Sciences
Seol Hwa Jo, Woo Hang Heo, Hye-Youn Son, Mingji Quan, Bok Sil Hong, Ju Hee Kim, Han-Byoel Lee, Wonshik Han, Yeonju Park, Dong-Sup Lee, Nam Hoon Kwon, Min Chul Park, Jeesoo Chae, Jong-Il Kim, Dong-Young Noh, Hyeong-Gon Moon
Summary: The direct co-culture of breast cancer cells with non-tumorigenic mammary epithelial cells leads to substantial changes in the molecular and functional characteristics of the mammary epithelial cells, with enhanced proliferation, migration, colony formation, and sphere formation capabilities. Dysregulation of cancer-related pathways is observed, along with upregulation of S100A8 and S100A9, suggesting a potential transition program mediated by these proteins in non-tumorigenic epithelial cells.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Maria Perez-Lanzon, Vincent Carbonnier, Pierre Cordier, Fatima Domenica Elisa De Palma, Adriana Petrazzuolo, Christophe Klein, Floriane Arbaretaz, Khady Mangane, Gautier Stoll, Isabelle Martins, Helene Fohrer Ting, Juliette Paillet, Sophie Mouillet-Richard, Delphine Le Corre, Wenjjin Xiao, Marine Sroussi, Chantal Desdouets, Pierre Laurent-Puig, Jonathan Pol, Carlos Lopez-Otin, Maria Chiara Maiuri, Guido Kroemer
Summary: The study successfully established a new breast cancer cell line B6BC, which can be transplanted in C57BL/6 mice and mimics the extravasation of GFP-tagged cancer cells in blood circulation. B6BC-derived tumors are resistant to PD-1 immunotherapy but show good response to ER antagonists and anthracycline-based chemotherapy, suggesting potential new treatment strategies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Tao Lu, Lisa Oomens, Leon W. M. M. Terstappen, Jai Prakash
Summary: Cancer-associated fibroblasts (CAFs) are important drivers in the tumor microenvironment and facilitate the growth and survival of tumor cells, as well as metastasis formation. In this study, we aimed to study circulating CAFs (cCAFs) and circulating tumor cells (CTCs) in a preclinical breast tumor model in mice in order to understand the effect of chemotherapy on cCAFs and CTC formation. We found that tumors with CAFs grew faster than tumors without CAFs. Furthermore, chemotherapy may exacerbate the formation of cCAFs and CTCs, which may eventually support the formation of a metastasis niche in breast cancer.
Article
Oncology
Saverio Gentile, Najmeh Eskandari, Michael A. Rieger, Bruce D. Cuevas
Summary: MEKK1 plays a role in regulating stroma cell gene expression and affects the function of breast tumor cells. Loss of MEKK1 leads to decreased ability of fibroblasts to induce tumor cell invasion, indicating its crucial role in the microenvironment that supports metastasis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qin Li, Hang Yuan, Gang Zhao, Jie Zhang, Siqi Li, Di Gong, Tianyu Feng, Qiming Kou, Qijing Wang, Guanru Wang, Shan Li, Kai Li, Ping Lin
Summary: Breast cancer is the leading cause of cancer-related deaths in women worldwide, and cancer-associated fibroblasts (CAFs) play a critical role in its progression. However, the detailed molecular mechanisms of CAF activation are still unclear. This study found that loss of ZNF32 promotes the activation of CAFs, leading to increased growth and metastasis of breast cancer cells. Mechanistically, ZNF32 inhibits TGFB1 transcription, preventing fibroblast activation. This study implicates ZNF32 as a potential therapeutic target against breast cancer.
Review
Oncology
Mo Zhang, Zhixian Chen, Yan Wang, Hongbo Zhao, Yan Du
Summary: This review focuses on the important role of cancer-associated fibroblasts (CAFs) in the ovarian cancer tumor microenvironment. Different subtypes of CAFs have specific functions in tumor pathogenesis and can be potential treatment targets. Several clinical or preclinical trials have targeted CAFs to enhance ovarian cancer treatment outcomes.
Article
Oncology
Lauryn R. Werner, Katelin A. Gibson, Merit L. Goodman, Dominika E. Helm, Katherine R. Walter, Sean M. Holloran, Gloria M. Trinca, Richard C. Hastings, Howard H. Yang, Ying Hu, Junping Wei, Gangjun Lei, Xiao-Yi Yang, Rashna Madan, Alfredo A. Molinolo, Mary A. Markiewicz, Prabhakar Chalise, Margaret L. Axelrod, Justin M. Balko, Kent W. Hunter, Zachary C. Hartman, Carol A. Lange, Christy R. Hagan
Summary: Clinical studies have linked the use of progestins, synthetic progesterone, to an increased risk of breast cancer. However, the specific role of native progesterone signaling through the progesterone receptor in breast tumor formation remains poorly understood. Research suggests that progesterone can repress certain immune signaling pathways, potentially promoting tumor development in the mammary gland. This study investigated the effects of progesterone on immune cell populations in mouse mammary glands, as well as the impact of progesterone receptor overexpression on tumor formation and immune cell populations. The findings indicate that progesterone treatment and progesterone receptor overexpression are associated with inhibited immune responses, decreased immune cell populations, and an increased risk of mammary gland tumor development in mice.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Cell Biology
Jenny A. Rudnick, Teresa Monkkonen, Florie A. Mar, James M. Barnes, Hanna Starobinets, Juliet Goldsmith, Srirupa Roy, Sofia Bustamante Eguiguren, Valerie M. Weaver, Jayanta Debnath
Summary: Autophagy inhibitors are being explored for cancer treatment due to their ability to hinder tumor cell survival, while researchers are increasingly interested in how modulating autophagy in the host stroma affects tumorigenesis. Fibroblasts play key roles in cancer progression by promoting desmoplasia, with autophagy in stromal fibroblasts found to be crucial for mammary tumor growth.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Heather M. Brechbuhl, Mengyu Xie, Etana G. Kopin, Amy L. Han, Kiran Vinod-Paul, Jaime Hagen, Susan Edgerton, Philip Owens, Sharon Sams, Anthony Elias, Carol A. Sartorius, Aik-Choon Tan, Peter Kabos
Summary: The tumor microenvironment plays a crucial role in response and resistance to endocrine therapy in ER-positive breast cancer. The study found that neoadjuvant endocrine therapy alters TME composition, promoting the expansion of less favorable TASC(CDCP1) population associated with TME remodeling and increased immune infiltration supportive of tumor progression.
MOLECULAR CARCINOGENESIS
(2022)
Review
Cell Biology
Zhanhuai Wang, Qi Yang, Yinuo Tan, Yang Tang, Jun Ye, Bin Yuan, Wei Yu
Summary: Cancer-associated fibroblasts (CAFs) are heterogeneous cells in the tumor microenvironment that can both promote and inhibit tumor development. The activation state of CAFs can vary, leading to different roles in early-stage and advanced-stage cancer. Understanding the diverse functions and origins of CAFs is crucial for developing precise cancer therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Ralf-Peter Czekay, Dong-Joo Cheon, Rohan Samarakoon, Stacie M. Kutz, Paul J. Higgins
Summary: This review discusses the complex interactions between cancer-associated fibroblasts (CAFs) and other cell types in the tumor microenvironment and their impact on tumor development. The presence of CAFs and their secretion of factors contribute to tumor progression, metastasis, drug resistance, and relapse. Studying the pathways and genes involved in the interaction between CAFs and cells provides new targets and opportunities for cancer treatment.
Article
Biotechnology & Applied Microbiology
Jiaxuan Xia, Shuya Zhang, Ru Zhang, Anni Wang, Ying Zhu, Meichen Dong, Shaojie Ma, Chao Hong, Shengyao Liu, Dan Wang, Jianxin Wang
Summary: The use of Rg3 liposomes loaded with docetaxel (DTX) has shown improved chemotherapy effects on triple-negative breast cancer (TNBC) compared to conventional cholesterol liposomes. Rg3-Lp/DTX exhibited enhanced penetration at the tumor site and reversed the activation of cancer-associated fibroblasts (CAFs), reducing the stroma barrier. Therefore, Rg3-Lp/DTX shows promising therapeutic efficacy and a simple preparation process for TNBC treatment.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Review
Cell Biology
Deepshikha Mishra, Debabrata Banerjee
Summary: The cancer secretome is a collection of proteins released by cancer cells, which provides important information for cancer diagnosis and treatment. While previous studies have focused on the secretome of cancer cells, the contribution of stromal cells, particularly cancer-associated fibroblasts (CAFs), needs to be further explored. Investigating the secretome of CAFs can lead to the discovery of novel biomarkers and potential therapeutic targets, and enhance our understanding of personalized cancer treatment.
Article
Oncology
Carlo Sorrentino, Stefania Livia Ciummo, Luigi D'Antonio, Cristiano Fieni, Paola Lanuti, Alice Turdo, Matilde Todaro, Emma Di Carlo
Summary: IL30 plays a crucial role in regulating the viability and growth of breast cancer stem cells (BCSC) through juxtacrine signals and mediators such as CXCL10 and IL23. Targeting IL30 could potentially restrain the BCSC compartment and counteract breast cancer progression by disrupting its autocrine loops and immune subversion pathways.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Quentin Klopfenstein, Valentin Derangere, Laurent Arnould, Marion Thibaudin, Emeric Limagne, Francois Ghiringhelli, Caroline Truntzer, Sylvain Ladoire
Summary: The prognosis of early breast cancer is associated with the clinic-pathological stage and the molecular characteristics of tumor cells. In some patients, the presence of tumor-infiltrating immune cells can impact long term outcome. A new gene expression deconvolution algorithm was developed to estimate immune cell populations in tumors and found that myeloid cells were associated with poor outcomes, while lymphoid cells were linked to favorable prognosis. This information, when combined with clinical stage and PAM50, can improve the prediction of relapse or death in early breast cancer patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Shasha Yin, Liu Liu, Charles Brobbey, Viswanathan Palanisamy, Lauren E. Ball, Shaun K. Olsen, Michael C. Ostrowski, Wenjian Gan
Summary: AKT is involved in key cellular processes, and arginine methylation by PRMT5 promotes AKT activity and tumorigenesis.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Denys Rujchanarong, Julia Lefler, Janet E. Saunders, Sarah Pippin, Laura Spruill, Jennifer R. Bethard, Lauren E. Ball, Anand S. Mehta, Richard R. Drake, Michael C. Ostrowski, Peggi M. Angel
Summary: This study introduces a novel approach that combines immunohistochemistry with extracellular matrix imaging mass spectrometry to analyze ECM proteins based on patterns of cell types in tissue. The research also delves into the regulation and expression of collagen within breast stroma, shedding light on its role in cancer progression.
Editorial Material
Biochemistry & Molecular Biology
Allison T. Scott, Cassandra J. Vondrak, Allen G. Sanderlin, Rebecca L. Lamason
Summary: Rickettsia parkeri is an intracellular bacterial pathogen that primarily targets vascular endothelial cells. It is transmitted by tick vectors and causes a milder form of disease compared to other spotted fever group Rickettsia.
TRENDS IN MICROBIOLOGY
(2022)
Article
Oncology
Said M. Elshafae, Nicole A. Kohart, Justin T. Breitbach, Blake E. Hildreth, Thomas J. Rosol
Summary: Adult T-cell leukemia (ATL) is an aggressive leukemia associated with HTLV-1 infection, with dysregulated histone deacetylases implicated in its pathogenesis. This study found that AR-42 and Zol reduced ATL cell viability and decreased tumor growth in vitro and in vivo. Targeting both ATL cells and bone osteoclasts with HDACi and bisphosphonates could be a promising approach to reducing bone tumor burden in ATL patients.
Article
Medicine, Research & Experimental
Yaoling Shu, Faizule Hassan, Michael C. Ostrowski, Kamal D. Mehta
Summary: Hepatic PKC beta deficiency slows disposal of glucose overload by suppressing glycogenesis and increasing hepatic glucose output, leading to lower plasma glucose levels and improved systemic glucose tolerance. This involves upregulating glucokinase and activating glycogen synthase to redirect more glucose-6-phosphate to glycogen synthesis.
Meeting Abstract
Biochemistry & Molecular Biology
Shiyu Yuan, Noriko Kantake, Said M. Elshafae, Thomas J. Rosol
Article
Oncology
Jinghai Wu, Xin Liu, Julie A. Wallace Reeser, Anthony J. Trimboli, Thierry Pecot, Gina M. Sizemore, Shan K. Naidu, Soledad A. Fernandez, Lianbo Yu, Michael Hallett, Morag Park, Gustavo W. Leone, Blake E. Hildreth, Michael C. Ostrowski
Summary: This study found that stroma-specific loss of p53 enhances tumorigenesis driven by the oncogene Kras(G12D) in mammary glands. The loss of p53 in the stroma promotes both epithelial and fibroblast proliferation, increases DNA damage and/or replication stress in tumor cells, and decreases apoptosis. Furthermore, it affects the tumor immune landscape and has an impact on patient survival.
MOLECULAR CANCER RESEARCH
(2022)
Article
Microbiology
Allen G. Sanderlin, Ruth E. Hanna, Rebecca L. Lamason
Summary: This study reveals the importance of the ankyrin repeat protein RARP-1 in host cell invasion and growth in Rickettsia infection. Contrary to previous studies suggesting secretion of RARP-1 into the host cytoplasm, this study shows that RARP-1 in R. parkeri resides in the periplasm and plays a critical role in the rickettsial life cycle.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biology
Julia E. Lefler, Catherine B. MarElia-Bennett, Katie A. Thies, Blake E. Hildreth, Sudarshana M. Sharma, Jason R. Pitarresi, Lu Han, Caroline Everett, Christopher Koivisto, Maria C. Cuitino, Cynthia Timmers, Elizabeth O'Quinn, Melodie Parrish, Martin J. Romeo, Amanda J. Linke, G. Aaron Hobbs, Gustavo Leone, Denis C. Guttridge, Teresa A. Zimmers, Gregory B. Lesinski, Michael C. Ostrowski
Summary: Disruption of the STAT3 signaling axis in stromal fibroblasts through genetic ablation of Stat3 slows tumor progression, increases survival, and reshapes the immune-suppressive tumor micro-environment in a PDAC mouse model. Loss of the tumor suppressor PTEN in pancreatic CAFs leads to increased STAT3 phosphorylation and promotes secretion of CXCL1.
LIFE SCIENCE ALLIANCE
(2022)
Article
Veterinary Sciences
Matthew R. Berry, Bahaa A. Fadl-Alla, Jonathan Samuelson, Thomas J. Rosol, Timothy M. Fan
Summary: This study investigates the expression of PSMA in canine iUC and PCA cell lines and archived patient samples, and finds no differential expression between the two types of cancer. Additionally, it identifies vinblastine as a potential effective chemotherapeutic agent for uroepithelial carcinomas.
BMC VETERINARY RESEARCH
(2022)
Article
Food Science & Technology
Ivonne M. C. M. Rietjens, Samuel M. Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J. Gooderham, F. Peter Guengerich, Stephen S. Hecht, Thomas J. Rosol, Jeanne M. Davidsen, Christie L. Harman, Sean V. Taylor
Summary: The FEMA Expert Panel program has evaluated the safety of NFCs used in food and published an updated procedure. The GRAS status of NFCs with propenylhydroxybenzene and allylalkoxybenzene constituents has been affirmed under their intended use as flavoring ingredients. The evaluation includes relevant data on absorption, metabolism, genotoxic potential, and toxicology.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Multidisciplinary Sciences
Lu Han, Yongxia Wu, Kun Fang, Sean Sweeney, Ulyss K. Roesner, Melodie Parrish, Khushbu Patel, Tom Walter, Julia Piermattei, Anthony Trimboli, Julia Lefler, Cynthia D. Timmers, Xue-Zhong Yu, Victor X. X. Jin, Michael T. Zimmermann, Angela J. Mathison, Raul Urrutia, Michael C. Ostrowski, Gustavo Leone
Summary: Through lineage tracing and single-cell RNA sequencing in mice, this study identifies the splanchnic mesenchyme as the tissue of origin for cancer-associated fibroblasts (CAFs) in pancreatic cancer. The findings shed light on pancreatic morphogenesis and tumorigenesis, and highlight the persistent transcriptional program underlying splanchnic lineage differentiation.
NATURE COMMUNICATIONS
(2023)
Article
Food Science & Technology
Jeanne M. Davidsen, Samuel M. Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J. Gooderham, F. Peter Guengerich, Stephen S. Hecht, Ivonne M. C. M. Rietjens, Thomas J. Rosol, Christie L. Harman, Danarubini Ramanan, Sean Taylor
Summary: The Flavor and Extract Manufacturers Association (FEMA) Expert Panel has re-evaluated the safety of Asafetida Oil (Ferula assa-foetida L.) FEMA 2108, Garlic Oil (Allium sativum L.) FEMA 2503, and Onion Oil (Allium cepa L.) FEMA 2817 as flavorings in food using a scientific procedure. The evaluation includes a complete chemical characterization of the natural flavor complexes (NFCs), evaluation of intake using the toxicological concern concept, and review of metabolic, genotoxic potential, and toxicology data. Based on the evaluation, these oils were affirmed as generally recognized as safe (GRASa) for their intended use as flavor ingredients.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Oncology
Katie A. Thies, Matthew W. Cole, Rachel E. Schafer, Jonathan M. Spehar, Dillon S. Richardson, Sarah A. Steck, Manjusri Das, Arthur W. Lian, Alo Ray, Reena Shakya, Sue E. Knoblaugh, Cynthia D. Timmers, Michael C. Ostrowski, Arnab Chakravarti, Gina M. Sizemore, Steven T. Sizemore
Summary: The study revealed important but paradoxical roles for RALA and RALB in the pathogenesis of TNBC, with RALA being identified as a potential precise treatment target for metastatic TNBC.
BREAST CANCER RESEARCH
(2021)
Meeting Abstract
Oncology
Julia E. Lefler, Katie MarElia, Michael C. Ostrowski