Type-3 Hyaluronan Synthase Attenuates Tumor Cells Invasion in Human Mammary Parenchymal Tissues
Wen-Jui Lee,
Shih-Hsin Tu,
Tzu-Chun Cheng,
Juo-Han Lin,
Ming-Thau Sheu,
Ching-Chuan Kuo,
Chun A. Changou,
Chih-Hsiung Wu,
Hui-Wen Chang,
Hang-Lung Chang,
Li-Ching Chen,
Yuan-Soon Ho
Affiliations
Wen-Jui Lee
Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Shih-Hsin Tu
Breast Medical Center, Taipei Medical University Hospital, Taipei 110, Taiwan
Tzu-Chun Cheng
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Juo-Han Lin
Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan
Ming-Thau Sheu
Department of Pharmaceutical Sciences, Taipei Medical University, Taipei 110, Taiwan
Ching-Chuan Kuo
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 350, Taiwan
Chun A. Changou
The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Chih-Hsiung Wu
Department of General Surgery, En Chu Kong Hospital, New Taipei City 110, Taiwan
Hui-Wen Chang
Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
Hang-Lung Chang
Department of General Surgery, En Chu Kong Hospital, New Taipei City 237, Taiwan
Li-Ching Chen
Breast Medical Center, Taipei Medical University Hospital, Taipei 110, Taiwan
Yuan-Soon Ho
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms.
