Cancer Cell Communications, Metastasis and Survival in Host Microenvironment

Dear Colleagues,

Cancer metastasis is responsible for approximately 90% cancer death [1]. When an invading cancer cell migrates out of the primary solid tumor, this cell faces unfriendly host cells in the microenvironment [2,3]. WW domain-containing oxidoreductase (WWOX)-deficient or-dysfunctional cancer cells, designated WWOXd [2,3], are mainly metastatic, and cannot recognize host cells and parental cancer cells. These metastatic cancer cells are able to dodge, compromise, and cause damage to the WWOX-functional normal host cells or parental cancer cells (WWOXf) from a distance [2,3]. WWOXf cells are either normal cells or benign cancer cells [2,3].

WWOXf cells migrate collectively and expel the individually migrating WWOXd cells. WWOXd cells, in turn, kill a portion of WWOXf cells from a distance by significantly upregulating redox activity in WWOXf cells for leading to cell death [2,3]. It is reasonable to assume that metastatic WWOXd cells are repelled, in part, by the parental WWOXf cells in the primary tumor, and then leave the home base. From a remote distance, WWOXf cells induce WWOXd cells to activate MIF, Hyal-2, Eph, and Wnt signaling pathways, followed by converging to the MEK/ERK signaling that enables WWOXd cells to undergo retrograde migration to evade WWOXf cells [2,3]. Exogenous TGF-β assists WWOXd cells to migrate forward in a collective manner and then merge with WWOXf cells, suggesting that TGF-β derived from metastatic WWOXd cells enhances the recognition and merging between WWOXd and WWOXf cell [2,3].

In this call for research and review papers 2023, the specific topic will focus on gene alterations that contribute to changes in cancer cell migratory behavior, cell-to-cell recognition and communication, cancer cell-host cell functional antagonism, and cell survival in host microenvironment. We welcome articles related, but not limited, to:

1. gene alteration-induced cancer cell metastasis and the underlined signaling pathways;
2. metastatic cancer cell and host cell recognition;
3. metastatic cancer cell modification of host microenvironment;
4. cancer cell-derived cytokines and/or exosomes in attacking host cells;
5. molecular mechanisms by which host cells fight back to kill metastatic cancer cells;
6. whether and how metastatic cancer cells and host cells compromise each other so that metastatic cancer cells can build a new home base in a target organ;
7. innovative methodologies to measure metastatic cancer cell and host cell recognition and communication.  

References

1. Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target Ther. 2020, 5, 28.
2. Chen, Y.A.; Sie, Y.D.; Liu, T.Y.; Kuo, H.L.; Chou, P.Y.; Chen, Y.J.; Lee, K.T.; Chen, P.J.; Chen, S.T.; Chang, N.S. Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299. Commun. Biol. 2021, 4, 1–19.
3. Chou, P.Y.; Lai, F.J.; Chen, Y.A.; Sie, Y.D.; Kuo, H.L.; Su, W.P.; Wu, C.Y.; Liu, T.Y.; Wen, K.Y.; Hsu, L.J.; et al. Strategies by which WWOX-deficient metastatic cancer cells utilize to survive via dodging, compromising, and causing damage to WWOX-positive normal microenvironment. Cell Death Discov. 2019, 5, 97.

Dr. Nan-Shan Chang
Guest Editor

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• cancer cells
• cancer cell-derived cytokines
• host microenvironment
• metastasis
• gene alteration
• signaling pathways
• host cells

Title: Label-free multimodal nonlinear optical microscopy combined with machine learning analysis of tissue microarrays to unveil host tumor-microenvironment interactions
Authors: Guan-Yu Zhuo
Affiliation: Institute of New Drug Development, China Medical University, Taichung, Taiwan
Abstract: Cancer progression and metastasis are intricately linked to the complex interactions between tumor cells and their microenvironment. This study introduces a novel approach to investigate these interactions using multimodal nonlinear optical microscopy combined with machine learning techniques. We employ second harmonic generation (SHG), third harmonic generation (THG) and two-photon fluorescence (TPF) imaging to analyze label-free normal and cancerous tissue microarrays containing comprehensive data from 500 patients provided by the National Cancer Institute (Bethesda, MD, USA). Our methodology leverages the unique capabilities of SHG, THG and TPEF to visualize extracellular matrix components and cellular structures without the need for exogenous labels or stains. This approach not only preserves the native tissue architecture but also reveals critical information about the tumor microenvironment that may be obscured by traditional histopathological techniques. To extract meaningful data from these high-resolution images, we implement machine learning algorithms, specifically the gray level co-occurrence matrix (GLCM) for tissue texture extraction and the support vector machine (SVM) for tissue classification. This integrative approach allows for the quantitative assessment of tissue morphology, cellular organization, and extracellular matrix composition, providing insights into cancer cell communication, metastatic potential, and survival mechanisms within the host microenvironment. Furthermore, this approach enables the identification of novel biomarkers and patterns associated with cancer progression and metastasis, providing great potential for enhancing our understanding of cancer biology, improving diagnostic accuracy, and ultimately contributing to the development of more effective therapeutic strategies related to the tumor microenvironment.