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Biology subjects

Hsieh, H.-T.

Publications and source records attributed to Hsieh, H.-T..

2 recordsLinked to original sources

Ganoderma formosanum polysaccharides enhance antitumor immune responses by downregulating the differentiation of myeloid-derived suppressor cells and tumor-associated macrophages

Ganoderma formosanum is a native species of Ganoderma isolated in Taiwan, and our previous studies showed that a polysaccharide fraction, PS-F2, purified from the submerged culture fluid of G. formosanum ATCC 76538 exhibited immunostimulatory and antitumor property. In the current study, we investigated the immunomodulatory and antitumor effects of PS-F2 from a UV-mutated G. formosanum variant NTU-1, which produced higher yields of PS-F2 than the original strain. Oral administration of PS-F2 effectively suppressed the growth of colon 26 (CT-26) carcinoma and splenomegaly in tumor-bearing mice without adversely affecting the animals health. We found that PS-F2 treatment resulted in augmented cytotoxic T lymphocyte (CTL) while significantly reducing the accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and regulatory T (Treg) cells in the spleen. In the tumor, PS-F2 treatment markedly enhanced CTL and Th1 responses, whereas it reduced the accumulation of tumor-associated macrophages (TAMs). Collectively, our data demonstrate that oral treatment of PS-F2 from G. formosanum NTU-1 in CT26 tumor-bearing mice activates antitumor immune responses and reduces the accumulation of immunosuppressive cells in the spleen and the tumor, leading to delayed tumor progression.

immunology↗

Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs [bEVs]; >200 nm, microvesicles) are less well explored. Here, we identify bEVs and sEVs as distinct EV populations, and determine that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence resonance energy transfer (BRET)-based EV reporter, reveals dose- dependent EV biodistribution at non-lethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, et individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass spectrometry (MS)- identified tumor progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include SLC29A1, CD9 and CD44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.

cancer biology↗