Lung Cancer-derived Galectin-1 Enhances Tumorigenic Potentiation of Tumor-associated Dendritic Cells by Expressing Heparin-binding EGF-like Growth Factor

Kuo, Po‐Lin; Huang, Ming‐Shyan; Cheng, Da-En; Hung, Jen‐Yu; Chou, Shah‐Hwa

doi:10.1074/jbc.m111.321190

Cited by 38 publications

(28 citation statements)

References 33 publications

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“…Research from our laboratory has recognized an essential role for Gal1 as an immunoevasive mechanism in human and mouse melanoma (9). These observations were further confirmed in mouse lung adenocarcinoma (10,11), and in human cancers including Hodgkin lymphoma (12,13), neuroblastoma (14), head and neck squamous cell carcinoma (15), pancreatic carcinoma (16), glioma (17), and T-cell lymphoma (18), suggesting that targeting the Gal1-glycan axis might contribute to overcome immunosuppression and potentiate immunotherapeutic approaches. Interestingly, Gal1 was identified as a tumor-associated protein capable of delineating the metastatic potential of human breast carcinoma (19,20).…”

Section: Introductionsupporting

confidence: 53%

“…This glycan-binding protein inhibits immune effector functions by shifting the balance toward a Th2 cytokine profile (9,23), by selectively deleting Th1 and Th17 cells (22) and by promoting the differentiation of tolerogenic dendritic cells (DC; refs. 11,14,26). Moreover, Gal1 facilitates the expansion of IL-10-producing T regulatory type-1 (Tr1) cells (23,26,27) and contributes to the immunosuppressive activity of CD4…”

Section: Introductionmentioning

confidence: 99%

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Targeting Galectin-1 Overcomes Breast Cancer-Associated Immunosuppression and Prevents Metastatic Disease

et al. 2013

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Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1 þ cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T reg cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. Cancer Res; 73(3); 1107-17. Ó2012 AACR.

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Section: Introductionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Targeting Galectin-1 Overcomes Breast Cancer-Associated Immunosuppression and Prevents Metastatic Disease

et al. 2013

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“…EGFR is activated in tumor-associated endothelial cells, but not in endothelial cells within uninvolved organ regions, suggesting that EGF receptor activation and expression of EGF receptors on endothelial cells is conditioned by the organ microenvironment (Kim et al , 2003). It is also believed that cancer cells secrete EGF-like growth factors that can act directly on endothelial cells (Kuo et al , 2012). The microenvironment can also send signals to tumor cells.…”

Section: Egfr Signaling In Normal and Transformed Cellsmentioning

confidence: 99%

Epidermal Growth Factor Signaling in Transformed Cells

Lindsey

Langhans

2015

International Review of Cell and Molecular Biology

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Members of the epidermal growth factor receptor (EGFR/ErbB) family play a critical role in normal cell growth and development. However, many ErbB family members, especially EGFR, are aberrantly expressed or deregulated in tumors and are thought to play crucial roles in cancer development and metastatic progression. In this chapter, we provide an overview of key mechanisms contributing to aberrant EGFR/ErbB signaling in transformed cells which results in many phenotypic changes associated with the earliest stages of tumor formation, including several hallmarks of epithelial-to-mesenchymal transition (EMT). These changes often occur through interaction with other major signaling pathways important to tumor progression resulting in a multitude of transcriptional changes that ultimately impact cell morphology, proliferation and adhesion, all of which are crucial for tumor progression. The resulting mesh of signaling networks will need to be taken into account as new regimens are designed for targeting EGFR for therapeutic intervention. As new insights into the molecular mechanisms of the cross-talk of EGFR signaling with other signaling pathways and their role in therapeutic resistance to anti-EGFR therapies are gained a continual reassessment of clinical therapeutic regimes and strategies will be required. Understanding the consequences and complexity of EGF signaling and how it relates to tumor progression is critical for the development of clinical compounds and establishing clinical protocols for the treatment of cancer.

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“…Conversely, DC isolated from non-small cell lung tumors can over express immuno-regulatory molecules such as PD-L1 52 and CD276 (a member of the B7 family also known as B7-H3) 53 and these are likely to be associated with a poor prognosis. Lung cancers can secrete galectin-1 that enhances DC production of heparin binding EGF-like growth factor which then increases cancer progression 54 . There is much interest in utilizing DC-based vaccines in combination with activated killer T-cells to enhance the host anti-tumor response in lung cancer.…”

Section: Lung Cancer and Mesotheliomamentioning

confidence: 99%