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Cells
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Crosstalk between the Bone Marrow Microenvironment and Breast Cancer
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Crosstalk between the Bone Marrow Microenvironment and Breast Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (10 August 2023) | Viewed by 10400

Special Issue Editor

Prof. Pranela Rameshwar

E-Mail Website
Guest Editor
Department of Medicine-Hematology/Oncology, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA
Interests: cytokines; breast cancer; exosomes; dormancy; aging; glioblastoma; hematopoiesis; miRNA; neural-hematopoiesis axis; stem cells

Special Issue Information

Dear Colleagues,

Breast cancer shows a preference for bone marrow, resulting in a poor prognosis. The cancer cells can survive as dormant cells for decades within the bone marrow microenvironment. These dormant breast cancer cells can resurge decades later into tertiary metastasis. The interaction between breast cancer cells and components of the marrow is complex. The marrow microenvironmental components could include combinations of cells, surface molecules such as connexion and integrins, nanotubes to transfer mitochondria, cytokine production to induce the production of other genes, and the release of microvesicles to transfer messages among cells. The contents of released microvesicles could change within different niches because of soluble secretome changes. For example, cytokines released from cancer cells could induce specific cargo within the microvesicles of bone marrow cells. These complex interactions between the cancer cells and bone marrow microenvironment lead to cancer cells showing functional and phenotypic changes, resulting in drug resistance, with the potential to become cancer stem cells. These changes in breast cancer cells occur as the cancer cells move across the marrow, starting upon entry into the marrow and as they move towards the endosteal region. A series of articles with inter- and multi-disciplinary approaches will provide insight into the changes occurring in the marrow. Scientific information will form the basis for developing novel treatments to target metastatic breast cancer cells without toxic effects on the normal marrow microenvironment.

Prof. Pranela Rameshwar
Guest Editor

Manuscript Submission Information

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Keywords

  • bone marrow
  • 3D cultures
  • breast cancer
  • dormancy
  • metastasis
  • secretome
  • microvesicle
  • stem cells

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Published Papers (3 papers)

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25 pages, 5665 KiB  
Article
The Revelation of Continuously Organized, Co-Overexpressed Protein-Coding Genes with Roles in Cellular Communications in Breast Cancer
by Aswathy Mary Paul, Revikumar Amjesh, Bijesh George, Deivendran Sankaran, Oleta A. Sandiford, Pranela Rameshwar, Madhavan Radhakrishna Pillai and Rakesh Kumar
Cells 2022, 11(23), 3806; https://doi.org/10.3390/cells11233806 - 28 Nov 2022
Cited by 3 | Viewed by 2271
Abstract
Many human cancers, including breast cancer, are polygenic and involve the co-dysregulation of multiple regulatory molecules and pathways. Though the overexpression of genes and amplified chromosomal regions have been closely linked in breast cancer, the notion of the co-upregulation of genes at a [...] Read more.
Many human cancers, including breast cancer, are polygenic and involve the co-dysregulation of multiple regulatory molecules and pathways. Though the overexpression of genes and amplified chromosomal regions have been closely linked in breast cancer, the notion of the co-upregulation of genes at a single locus remains poorly described. Here, we describe the co-overexpression of 34 continuously organized protein-coding genes with diverse functions at 8q.24.3(143437655-144326919) in breast and other cancer types, the CanCord34 genes. In total, 10 out of 34 genes have not been reported to be overexpressed in breast cancer. Interestingly, the overexpression of CanCord34 genes is not necessarily associated with genomic amplification and is independent of hormonal or HER2 status in breast cancer. CanCord34 genes exhibit diverse known and predicted functions, including enzymatic activities, cell viability, multipotency, cancer stem cells, and secretory activities, including extracellular vesicles. The co-overexpression of 33 of the CanCord34 genes in a multivariant analysis was correlated with poor survival among patients with breast cancer. The analysis of the genome-wide RNAi functional screening, cell dependency fitness, and breast cancer stem cell databases indicated that three diverse overexpressed CanCord34 genes, including a component of spliceosome PUF60, a component of exosome complex EXOSC4, and a ribosomal biogenesis factor BOP1, shared roles in cell viability, cell fitness, and stem cell phenotypes. In addition, 17 of the CanCord34 genes were found in the microvesicles (MVs) secreted from the mesenchymal stem cells that were primed with MDA-MB-231 breast cancer cells. Since these MVs were important in the chemoresistance and dedifferentiation of breast cancer cells into cancer stem cells, these findings highlight the significance of the CanCord34 genes in cellular communications. In brief, the persistent co-overexpression of CanCord34 genes with diverse functions can lead to the dysregulation of complementary functions in breast cancer. In brief, the present study provides new insights into the polygenic nature of breast cancer and opens new research avenues for basic, preclinical, and therapeutic studies in human cancer. Full article
(This article belongs to the Special Issue Crosstalk between the Bone Marrow Microenvironment and Breast Cancer)
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27 pages, 11203 KiB  
Article
Delineation of Pathogenomic Insights of Breast Cancer in Young Women
by Aswathy Mary Paul, Bijesh George, Sunil Saini, Madhavan Radhakrishna Pillai, Masakazu Toi, Luis Costa and Rakesh Kumar
Cells 2022, 11(12), 1927; https://doi.org/10.3390/cells11121927 - 15 Jun 2022
Cited by 7 | Viewed by 3713
Abstract
The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only [...] Read more.
The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment. Full article
(This article belongs to the Special Issue Crosstalk between the Bone Marrow Microenvironment and Breast Cancer)
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Other

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16 pages, 885 KiB  
Perspective
Bone Marrow-Derived Cells in Endometrial Cancer Pathogenesis: Insights from Breast Cancer
by Alejandra I. Ferrer, Ella Einstein and Sara S. Morelli
Cells 2022, 11(4), 714; https://doi.org/10.3390/cells11040714 - 17 Feb 2022
Cited by 2 | Viewed by 3422
Abstract
Endometrial cancer is the most common gynecological cancer, representing 3.5% of all new cancer cases in the United States. Abnormal stem cell-like cells, referred to as cancer stem cells (CSCs), reside in the endometrium and possess the capacity to self-renew and differentiate into [...] Read more.
Endometrial cancer is the most common gynecological cancer, representing 3.5% of all new cancer cases in the United States. Abnormal stem cell-like cells, referred to as cancer stem cells (CSCs), reside in the endometrium and possess the capacity to self-renew and differentiate into cancer progenitors, leading to tumor progression. Herein we review the role of the endometrial microenvironment and sex hormone signaling in sustaining EC progenitors and potentially promoting dormancy, a cellular state characterized by cell cycle quiescence and resistance to conventional treatments. We offer perspective on mechanisms by which bone marrow-derived cells (BMDCs) within the endometrial microenvironment could promote endometrial CSC (eCSC) survival and/or dormancy. Our perspective relies on the well-established example of another sex hormone-driven cancer, breast cancer, in which the BM microenvironment plays a crucial role in acquisition of CSC phenotype and dormancy. Our previous studies demonstrate that BMDCs migrate to the endometrium and express sex hormone (estrogen and progesterone) receptors. Whether the BM is a source of eCSCs is unknown; alternatively, crosstalk between BMDCs and CSCs within the endometrial microenvironment could be an additional mechanism supporting eCSCs and tumorigenesis. Elucidating these mechanisms will provide avenues to develop novel therapeutic interventions for EC. Full article
(This article belongs to the Special Issue Crosstalk between the Bone Marrow Microenvironment and Breast Cancer)
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