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Cancers
Special Issues
Molecular and Cellular Changes in the Formation of Tumor-Initiating Cells
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Molecular and Cellular Changes in the Formation of Tumor-Initiating Cells

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7050

Special Issue Editor

Dr. Zhe Li

E-Mail Website
Guest Editor
1. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
2. Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA
Interests: cellular origin of cancer; stem cell and cancer; premalignant and tumor microenvironment; mouse models of human cancer; developmental oncobiology; breast cancer; ovarian cancer; prostate cancer; mammary gland biology

Special Issue Information

Dear Colleagues,

Tumor-Initiating Cells (TICs), also known as Cancer Stem Cells, refer to a subset of cancer cells capable of self-renewal proliferation and producing all other cancer cell types within a tumor. The concept of TICs is originally a functional definition, largely based on transplantation assays. The term TICs is now more widely used in cancer biology, often referring to or overlapping with cellular origin of cancer, most recent common ancestor of cancer (based on sequencing data), cancer cells with stem cell-like properties, therapy-resistant cancer cells, or metastasis-initiating cells. Nevertheless, TICs represent a key subset of cancer cells responsible for cancer initiation, progression, metastasis, and therapy resistance; therefore, a better mechanistic understanding of their formation would be essential for developing novel strategies of cancer prevention and therapy, and for overcoming therapy resistance.

The purpose of this Special Issue is to define molecular and cellular changes leading to the formation of TICs, including 1) genetic basis and/or epigenetic mechanism of TIC formation; 2) contribution of environmental factors (e.g., immune cells) to TIC formation; 3) drug resistance and TICs; 4) formation of metastasis-initiating cells; 5) emerging technology for studying TICs. This Special Issue welcomes both original research articles and reviews.

Dr. Zhe Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer stem cell
  • stem cell and cancer
  • cellular origin of cancer
  • tumor microenvironment
  • immune mechanism
  • most recent common ancestor of cancer
  • metastasis-initiating cell
  • cellular basis of cancer therapy resistance
  • genetic and epigenetic basis of tumor initiation
  • tumor cell heterogeneity

Published Papers (3 papers)

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Research

Jump to: Review

12 pages, 1735 KiB  
Article
Use of Next Generation Sequencing to Define the Origin of Primary Myelofibrosis
by Giuseppe Visani, Maryam Etebari, Fabio Fuligni, Antonio Di Guardo, Alessandro Isidori, Federica Loscocco, Stefania Paolini, Mohsen Navari and Pier Paolo Piccaluga
Cancers 2023, 15(6), 1785; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15061785 - 15 Mar 2023
Cited by 1 | Viewed by 1671
Abstract
Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow sclerosis, extra-medullary hematopoiesis, and possible transformation to acute leukemia. In the last decade, the molecular pathogenesis of the disease has been largely uncovered. Particularly, genetic and genomic studies have [...] Read more.
Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow sclerosis, extra-medullary hematopoiesis, and possible transformation to acute leukemia. In the last decade, the molecular pathogenesis of the disease has been largely uncovered. Particularly, genetic and genomic studies have provided evidence of deregulated oncogenes in PMF as well as in other MPNs. However, the mechanisms through which transformation to either the myeloid or lymphoid blastic phase remain obscure. Particularly, it is still debated whether the disease has origins in a multi-potent hematopoietic stem cells or instead in a commissioned myeloid progenitor. In this study, we aimed to shed light upon this issue by using next generation sequencing (NGS) to study both myeloid and lymphoid cells as well as matched non-neoplastic DNA of PMF patients. Whole exome sequencing revealed that most somatic mutations were the same between myeloid and lymphoid cells, such findings being confirmed by Sanger sequencing. Particularly, we found 126/146 SNVs to be the e same (including JAK2V617F), indicating that most genetic events likely to contribute to disease pathogenesis occurred in a non-commissioned precursor. In contrast, only 9/27 InDels were similar, suggesting that this type of lesion contributed instead to disease progression, occurring at more differentiated stages, or maybe just represented “passenger” lesions, not contributing at all to disease pathogenesis. In conclusion, we showed for the first time that genetic lesions characteristic of PMF occur at an early stage of hematopoietic stem cell differentiation, this being in line with the possible transformation of the disease in either myeloid or lymphoid acute leukemia. Full article
(This article belongs to the Special Issue Molecular and Cellular Changes in the Formation of Tumor-Initiating Cells)
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15 pages, 3264 KiB  
Article
Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from Krt8+ Mesothelial and Müllerian-Derived Epithelial Cells
by Eun-Sil Park, Dongxi Xiang, Ying Xie, Roderick T. Bronson and Zhe Li
Cancers 2022, 14(3), 841; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030841 - 08 Feb 2022
Cited by 2 | Viewed by 1946
Abstract
Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or Müllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these [...] Read more.
Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or Müllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of Krt8 promoter (Ad-K8-Cre) to mice carrying combinations of various conditional alleles for cancer genes. We found that Ad-K8-Cre specifically targeted mesothelial cells, including ovarian surface epithelial (OSE) cells (mainly the LGR5+ subset of OSE cells) and mesothelial cells lining the fallopian tube (FT) serosa; the injected Ad-K8-Cre also targeted Müllerian-derived epithelial cells, including FT epithelial cells and uterine endometrial epithelial cells. The loss of p53 may preferentially affect Müllerian-derived epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies (upon KRAS-activation or APC-loss) or adenoma on the FT surface (upon DICER-loss). Overall, our data suggest that different Krt8+ mesothelial and epithelial cell types in the female reproductive system may have different sensitivities toward oncogenic mutations and, as a result, oncogenic events may dominantly determine the locations and types of the gynecological malignancies developed from them. Full article
(This article belongs to the Special Issue Molecular and Cellular Changes in the Formation of Tumor-Initiating Cells)
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Review

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18 pages, 1093 KiB  
Review
Innate Immune Program in Formation of Tumor-Initiating Cells from Cells-of-Origin of Breast, Prostate, and Ovarian Cancers
by Sen Han, Xueqing Chen and Zhe Li
Cancers 2023, 15(3), 757; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030757 - 26 Jan 2023
Cited by 2 | Viewed by 2210
Abstract
Tumor-initiating cells (TICs), also known as cancer stem cells (CSCs), are cancer cells that can initiate a tumor, possess self-renewal capacity, and can contribute to tumor heterogeneity. TICs/CSCs are developed from their cells-of-origin. In breast, prostate, and ovarian cancers, progenitor cells for mammary [...] Read more.
Tumor-initiating cells (TICs), also known as cancer stem cells (CSCs), are cancer cells that can initiate a tumor, possess self-renewal capacity, and can contribute to tumor heterogeneity. TICs/CSCs are developed from their cells-of-origin. In breast, prostate, and ovarian cancers, progenitor cells for mammary alveolar cells, prostate luminal (secretory) cells, and fallopian tube secretory cells are the preferred cellular origins for their corresponding cancer types. These luminal progenitors (LPs) express common innate immune program (e.g., Toll-like receptor (TLR) signaling)-related genes. Microbes such as bacteria are now found in breast, prostate, and fallopian tube tissues and their corresponding cancer types, raising the possibility that their LPs may sense the presence of microbes and trigger their innate immune/TLR pathways, leading to an inflammatory microenvironment. Crosstalk between immune cells (e.g., macrophages) and affected epithelial cells (e.g., LPs) may eventually contribute to formation of TICs/CSCs from their corresponding LPs, in part via STAT3 and/or NFκB pathways. As such, TICs/CSCs can inherit expression of innate-immunity/TLR-pathway-related genes from their cells-of-origin; the innate immune program may also represent their unique vulnerability, which can be explored therapeutically (e.g., by enhancing immunotherapy via augmenting TLR signaling). Full article
(This article belongs to the Special Issue Molecular and Cellular Changes in the Formation of Tumor-Initiating Cells)
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