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Cancers
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Tumor Microenvironment: Intercellular Communication
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Tumor Microenvironment: Intercellular Communication

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 6898

Special Issue Editor

Dr. Iljin Kim

E-Mail Website
Guest Editor
Department of Pharmacology, Inha University College of Medicine, Incheon 22212, Republic of Korea
Interests: hypoxia; cancer; extracellular vesicles; targeted protein degradation

Special Issue Information

Dear Colleagues,

The tumor microenvironment (TME) plays a crucial role in cancer progression, metastasis, and therapeutic resistance. It involves a complex interplay among tumor cells, stromal cells, immune cells, and the extracellular matrix. The intercellular communication and signal transduction that occurs within the TME are critical aspects of this interplay. This special issue of Cancers aims to provide a comprehensive overview of the key signaling molecules and pathways involved in these communication processes and their effects on tumor behavior. Additionally, we will publish reviews and original research that offer new insights into recent advances in targeting these signaling pathways for cancer treatment.

Dr. Iljin Kim
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 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

  • tumor microenvironment
  • stromal cells
  • immune cells
  • extracellular matrix
  • hypoxia
  • angiogenesis
  • intercellular communication
  • extracellular vesicles
  • cancer therapy

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Published Papers (3 papers)

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Research

Jump to: Review

13 pages, 3896 KiB  
Article
Fabrication of a Three-Dimensional Spheroid Culture System for Oral Squamous Cell Carcinomas Using a Microfabricated Device
by Reiko Ikeda-Motonakano, Fumika Hirabayashi-Nishimuta, Naomi Yada, Ryota Yamasaki, Yoshie Nagai-Yoshioka, Michihiko Usui, Kohji Nakazawa, Daigo Yoshiga, Izumi Yoshioka and Wataru Ariyoshi
Cancers 2023, 15(21), 5162; https://doi.org/10.3390/cancers15215162 - 26 Oct 2023
Cited by 1 | Viewed by 1769
Abstract
Cancer stem cells (CSCs) are considered to be responsible for recurrence, metastasis, and resistance to treatment in many types of cancers; therefore, new treatment strategies targeting CSCs are attracting attention. In this study, we fabricated a polyethylene glycol-tagged microwell device that enabled spheroid [...] Read more.
Cancer stem cells (CSCs) are considered to be responsible for recurrence, metastasis, and resistance to treatment in many types of cancers; therefore, new treatment strategies targeting CSCs are attracting attention. In this study, we fabricated a polyethylene glycol-tagged microwell device that enabled spheroid formation from human oral squamous carcinoma cells. HSC-3 and Ca9-22 cells cultured in the microwell device aggregated and generated a single spheroid per well within 24–48 h. The circular shape and smooth surface of spheroids were maintained for up to five days, and most cells comprising the spheroids were Calcein AM-positive viable cells. Interestingly, the mRNA expression of CSC markers (Cd44, Oct4, Nanog, and Sox2) were significantly higher in the spheroids than in the monolayer cultures. CSC marker-positive cells were observed throughout the spheroids. Moreover, resistance to cisplatin was enhanced in spheroid-cultured cells compared to that in the monolayer-cultured cells. Furthermore, some CSC marker genes were upregulated in HSC-3 and Ca9-22 cells that were outgrown from spheroids. In xenograft model, the tumor growth in the spheroid implantation group was comparable to that in the monolayer culture group. These results suggest that our spheroid culture system may be a high-throughput tool for producing uniform CSCs in large numbers from oral cancer cells. Full article
(This article belongs to the Special Issue Tumor Microenvironment: Intercellular Communication)
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Review

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28 pages, 3339 KiB  
Review
Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems
by Dragana Nikitovic, Ekaterina Kukovyakina, Aikaterini Berdiaki, Alexandros Tzanakakis, Anna Luss, Elizaveta Vlaskina, Anne Yagolovich, Aristides Tsatsakis and Andrey Kuskov
Cancers 2024, 16(22), 3768; https://doi.org/10.3390/cancers16223768 - 8 Nov 2024
Cited by 1 | Viewed by 2467
Abstract
Chemotherapy remains the primary therapeutic approach in treating cancer. The tumor microenvironment (TME) is the complex network surrounding tumor cells, comprising various cell types, such as immune cells, fibroblasts, and endothelial cells, as well as ECM components, blood vessels, and signaling molecules. The [...] Read more.
Chemotherapy remains the primary therapeutic approach in treating cancer. The tumor microenvironment (TME) is the complex network surrounding tumor cells, comprising various cell types, such as immune cells, fibroblasts, and endothelial cells, as well as ECM components, blood vessels, and signaling molecules. The often stiff and dense network of the TME interacts dynamically with tumor cells, influencing cancer growth, immune response, metastasis, and resistance to therapy. The effectiveness of the treatment of solid tumors is frequently reduced due to the poor penetration of the drug, which leads to attaining concentrations below the therapeutic levels at the site. Cell-penetrating peptides (CPPs) present a promising approach that improves the internalization of therapeutic agents. CPPs, which are short amino acid sequences, exhibit a high ability to pass cell membranes, enabling them to deliver drugs efficiently with minimal toxicity. Specifically, the iRGD peptide, a member of CPPs, is notable for its capacity to deeply penetrate tumor tissues by binding simultaneously integrins ανβ3/ανβ5 and neuropilin receptors. Indeed, ανβ3/ανβ5 integrins are characteristically expressed by tumor cells, which allows the iRGD peptide to home onto tumor cells. Notably, the respective dual-receptor targeting mechanism considerably increases the permeability of blood vessels in tumors, enabling an efficient delivery of co-administered drugs or nanoparticles into the tumor mass. Therefore, the iRGD peptide facilitates deeper drug penetration and improves the efficacy of co-administered therapies. Distinctively, we will focus on the iRGD mechanism of action, drug delivery systems and their application, and deliberate future perspectives in developing iRGD-conjugated therapeutics. In summary, this review discusses the potential of iRGD in overcoming barriers to drug delivery in cancer to maximize treatment efficiency while minimizing side effects. Full article
(This article belongs to the Special Issue Tumor Microenvironment: Intercellular Communication)
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18 pages, 1086 KiB  
Review
Immune Cells in the Tumor Microenvironment of Soft Tissue Sarcomas
by Enar Jumaniyazova, Anastasiya Lokhonina, Dzhuliia Dzhalilova, Anna Kosyreva and Timur Fatkhudinov
Cancers 2023, 15(24), 5760; https://doi.org/10.3390/cancers15245760 - 8 Dec 2023
Cited by 5 | Viewed by 2064
Abstract
Soft tissue sarcomas (STSs) are a rare heterogeneous group of malignant neoplasms characterized by their aggressive course and poor response to treatment. This determines the relevance of research aimed at studying the pathogenesis of STSs. By now, it is known that STSs is [...] Read more.
Soft tissue sarcomas (STSs) are a rare heterogeneous group of malignant neoplasms characterized by their aggressive course and poor response to treatment. This determines the relevance of research aimed at studying the pathogenesis of STSs. By now, it is known that STSs is characterized by complex relationships between the tumor cells and immune cells of the microenvironment. Dynamic interactions between tumor cells and components of the microenvironment enhance adaptation to changing environmental conditions, which provides the high aggressive potential of STSs and resistance to antitumor therapy. Today, active research is being conducted to find effective antitumor drugs and to evaluate the possibility of using therapy with immune cells of STS. The difficulty in assessing the efficacy of new antitumor options is primarily due to the high heterogeneity of this group of malignant neoplasms. Studying the role of immune cells in the microenvironment in the progression STSs and resistance to antitumor therapies will provide the discovery of new biomarkers of the disease and the prediction of response to immunotherapy. In addition, it will help to initially divide patients into subgroups of good and poor response to immunotherapy, thus avoiding wasting precious time in selecting the appropriate antitumor agent. Full article
(This article belongs to the Special Issue Tumor Microenvironment: Intercellular Communication)
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