Galectin‑9 suppresses the tumor growth of colon cancer <i>in vitro</i> and <i>in vivo</i>

Morishita, Asahiro; Nomura, Kei; Tani, Joji; Fujita, Koji; Iwama, Hisakazu; Takuma, Kei; Nakahara, Masaru; Tadokoro, Tomoko; Oura, Kyoko; Chiyo, Taiga; Fujihara, Shintaro; Niki, Toshiro; Hirashima, Mitsuomi; Nishiyama, Akira; Himoto, Takashi; Masaki, Tsutomu

doi:10.3892/or.2021.8056

Cited by 21 publications

(19 citation statements)

References 55 publications

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“…For instance, the loss of Gal-9 expression is closely associated with tumor progression and metastasis formation in various epithelial cancers [ 3 , 4 , 5 ]. Further, (re)expression of Gal-9 in cells or treatment with recombinant Gal-9 suppresses cell proliferation and tumor growth in various cancers including breast cancer [ 3 ], hepatocellular carcinoma [ 6 ], cholangiocarcinoma [ 7 ], and colon cancer [ 8 ]. This cytotoxicity in colon cancer is independent of caspases and characterized by autophagosome accumulation and lysosomal swelling [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

et al. 2021

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In earlier studies, galectin-9 (Gal-9) was identified as a multifaceted player in both adaptive and innate immunity. Further, Gal-9 had direct cytotoxic and tumor-selective activity towards cancer cell lines of various origins. In the current study, we identified that treatment with Gal-9 triggered pronounced membrane alterations in cancer cells. Specifically, phosphatidyl serine (PS) was rapidly externalized, and the anti-phagocytic regulator, CD47, was downregulated within minutes. In line with this, treatment of mixed neutrophil/tumor cell cultures with Gal-9 triggered trogocytosis and augmented antibody-dependent cellular phagocytosis of cancer cells. Interestingly, this pro-trogocytic effect was also due to the Gal-9-mediated activation of neutrophils with upregulation of adhesion markers and mobilization of gelatinase, secretory, and specific granules. These activation events were accompanied by a decrease in cancer cell adhesion in mixed cultures of leukocytes and cancer cells. Further, prominent cytotoxicity was detected when leukocytes were mixed with pre-adhered cancer cells, which was abrogated when neutrophils were depleted. Taken together, Gal-9 treatment potently activated neutrophil-mediated anticancer immunity, resulting in the elimination of epithelial cancer cells.

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Section: Introductionmentioning

confidence: 99%

Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

et al. 2021

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“…The following day, 10 mg/mL of 5-FC was added to the drinking water of half of the mice (six UC-ACD-AF, six UC-CD-AF, and six ACD-AF), while for the other half of the mice the drinking water did not contain with 5-FC (six UC-ACD-AF, six UC-CD-AF, and six PBS). The tumor size was measured twice per week by digital calipers for the next 28 days (4 weeks), and the tumor volume was measured by the formula: 0.5 × (length × breadth 2 ). − The mice in different treatment groups were euthanized with CO 2 asphyxiation, when the total tumor volume in each mouse reached 2 cm 3 , which was considered as an end point. The average rate of tumor growth was then determined from the TumGrowth software …”

Section: Methodsmentioning

confidence: 99%

Enzyme Prodrug Therapy with Photo-Cross-Linkable Anti-EGFR Affibodies Conjugated to Upconverting Nanoparticles

et al. 2022

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In this work, we demonstrate that a photo-crosslinkable conjugate of upconverting nanoparticles and cytosine deaminase can catalyze prodrug conversion specifically at tumor sites in vivo. Non-covalent association of proteins and peptides with cellular surfaces leads to receptor-mediated endocytosis and catabolic degradation. Recently, we showed that covalent attachment of proteins such as affibodies to cell receptors yields extended expression on cell surfaces with preservation of protein function. To adapt this technology for in vivo applications, conjugates were prepared from upconverting nanoparticles and fusion proteins of affibody and cytosine deaminase enzyme (UC-ACD). The affibody allows covalent photo-cross-linking to epidermal growth factor receptors (EGFRs) overexpressed on Caco-2 human colorectal cancer cells under near-infrared (NIR) light. Once bound, the cytosine deaminase portion of the fusion protein converts the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU). NIR covalent photoconjugation of UC-ACD to Caco-2 cells showed 4-fold higher retention than observed with cells that were not irradiated in vitro. Next, athymic mice expressing Caco-2 tumors showed 5-fold greater UC-ACD accumulation in the tumors than either conjugates without the CD enzyme or UC-ACDs in the absence of NIR excitation. With oral administration of 5-FC prodrug, tumors with photoconjugated UC-ACD yielded 2-fold slower growth than control groups, and median mouse survival increased from 28 days to 35 days. These experiments demonstrate that enzyme-decorated nanoparticles can remain viable after a single covalent photoconjugation in vivo, which can in turn localize prodrug conversion to tumor sites for multiple weeks.

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“…In CRC miR-1246 inhibits Gal-9 and CCNG2, which is a tumor suppressor; decreased expression of CCNG2 occurs in many types of cancer and correlates with lymph node metastasis, clinical stage, and poor prognosis [ 121 , 163 ].…”

Section: Mirnas As Regulators Of Ics and Targeted Therapy Genesmentioning

confidence: 99%

The Features of Immune Checkpoint Gene Regulation by microRNA in Cancer

Kipkeeva

Музаффарова

Korotaeva

et al. 2022

IJMS

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Currently, the search for new promising tools of immunotherapy continues. In this regard, microRNAs (miRNAs) that influence immune checkpoint (IC) gene expression in tumor and T-cells and may be important regulators of immune cells are considered. MiRNAs regulate gene expression by blocking mRNA translation. An important feature of miRNA is its ability to affect the expression of several genes simultaneously, which corresponds to the trend toward the use of combination therapy. The article provides a list of miRNAs acting simultaneously on several ICs and miRNAs that, in addition to IC, can regulate the expression of targeted therapy genes. There is dependence of miRNA interactions with IC genes on the type of cancer. The analysis of the accumulated data demonstrates that only about 14% (95% CI: 9.8–20.1%) of the studied miRNAs regulate the expression of specific IC in more than one type of cancer. That is, there is tumor specificity in the miRNA action on ICs. A number of miRNAs demonstrated high efficiency in vitro and in vivo. This indicates the potential of miRNAs as promising agents for cancer immunotherapy. Additional studies of the miRNA–gene interaction features and the search for an optimal miRNA mimic structure are necessary.

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Galectin‑9 suppresses the tumor growth of colon cancer in vitro and in vivo

Cited by 21 publications

References 55 publications

Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Enzyme Prodrug Therapy with Photo-Cross-Linkable Anti-EGFR Affibodies Conjugated to Upconverting Nanoparticles

The Features of Immune Checkpoint Gene Regulation by microRNA in Cancer

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