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Tumor Microenvironments: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2390

Special Issue Editor

Dr. Sonam Mittal

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA
Interests: molecular mechanisms in cancer

Special Issue Information

Dear Colleagues,

Premetastatic niche formation is the chief event that confers the ability of colonization to tumor cells to distant locations for further metastasis. In the complex tumor microenvironment (TME), several malignant and non-malignant cell types, as well as components of the extracellular matrix (ECM), interact together to promote the metastatic process. Stromal cells, which are already present in the TME, are recruited from distant sites and “educated” by cancer cells through a dynamic crosstalk involving growth factors, cytokines, chemokines, miRNAs, and exosomes. Modulating the microenvironment is a key strategy by which many tumors evade host immune response as well as a variety of therapeutic drugs. Understanding the interaction between the tumor cells and their microenvironment can improve tumor intervention strategies.

The present Special Issue, titled “Tumor Microenvironments: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression”, aims to recent research developments to the wider community involved in this field. We welcome contributions on the topic outlined above.

Dr. Sonam Mittal
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • metastasis
  • metabolism
  • cytokines
  • cancer-derived extracellular vesicles
  • metabolic reprogramming

Published Papers (2 papers)

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Research

17 pages, 2357 KiB  
Article
Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer
by Kevin M. Sullivan, Haiqing Li, Annie Yang, Zhifang Zhang, Ruben R. Munoz, Kelly M. Mahuron, Yate-Ching Yuan, Isaac Benjamin Paz, Daniel Von Hoff, Haiyong Han, Yuman Fong and Yanghee Woo
Int. J. Mol. Sci. 2024, 25(7), 4117; https://doi.org/10.3390/ijms25074117 - 8 Apr 2024
Cited by 1 | Viewed by 876
Abstract
A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived [...] Read more.
A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients. Full article
(This article belongs to the Special Issue Tumor Microenvironments: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression)
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14 pages, 8069 KiB  
Article
Overexpression of RAB27A in Oral Squamous Cell Carcinoma Promotes Tumor Migration and Invasion via Modulation of EGFR Membrane Stability
by Jue Huang, Jie-Gang Yang, Jian-Gang Ren, Hou-Fu Xia, Gao-Hong Chen, Qiu-Yun Fu, Lin-Zhou Zhang, Hai-Ming Liu, Kui-Ming Wang, Qi-Hui Xie and Gang Chen
Int. J. Mol. Sci. 2023, 24(17), 13103; https://doi.org/10.3390/ijms241713103 - 23 Aug 2023
Cited by 2 | Viewed by 1051
Abstract
Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression [...] Read more.
Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression of RAB27A was assessed through immunohistochemical analysis utilizing tissue microarrays. In vitro experiments were conducted using RAB27A-knockdown cells to investigate its impact on OSCC tumor cells. Additionally, transcriptome sequencing was performed to elucidate potential underlying mechanisms. RAB27A was significantly overexpressed in OSCC, and particularly in metastatic lymph nodes. It was positively correlated with the clinical progression and poor survival prognosis. Silencing RAB27A notably decreased the proliferation, migration, and invasion abilities of OSCC cells in vitro. A Gene Ontology (GO) enrichment analysis indicated a strong association between RAB27A and the epidermal growth factor receptor (EGFR) signaling pathway. Further investigations revealed that RAB27A regulated the palmitoylation of EGFR via zinc finger DHHC-type containing 13 (ZDHHC13). These findings provide insights into OSCC progression and highlight RAB27A as a potential therapeutic target for combating this aggressive cancer. Full article
(This article belongs to the Special Issue Tumor Microenvironments: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression)
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