Cancer exosomes are 'micro factories' that aid in tumor growth
MD Anderson News Release October 23, 2014
Tiny nano-sized particles may play a major role in detecting and tracking breast cancer
MD Anderson News Release 10/23/2014
Exosomes, tiny, virus-sized particles released by cancer cells, can bioengineer micro-RNA (miRNA) molecules resulting in tumor growth. They do so with the help of proteins, such as one named Dicer. New research from The University of Texas MD Anderson Cancer Center suggests Dicer may also serve as a biomarker for breast cancer and possibly open up new avenues for diagnosis and treatment. Results from the investigation were published in today’s issue of Cancer Cell.
“Exosomes derived from cells and blood serum of patients with breast cancer, have been shown to initiate tumor growth in non-tumor-forming cells when Dicer and other proteins associated with the development of miRNAs are present,” said Raghu Kalluri, M.D., Ph.D., chair of the department of cancer biology at MD Anderson. “These findings offer opportunities for the development of exosomes-based biomarkers and shed insight into the mechanisms of how cancer spreads.”
Exosomes are small vesicles consisting of DNA, RNA and proteins enclosed in a membranes made up of two lipid layers. They perform specialized functions such as coagulation, intercellular signaling and cell “waste management.” They are shed into bodily fluids forming a source of disease-specific nucleic acids and proteins. Increasingly, exosomes are studied for their potential as both indicators of disease, and as a prospective new treatment approach.
All exosomes contain a cellular stew of smaller components including proteins, messenger RNA (mRNA) and miRNAs. Kalluri’s team reported that breast cancer associated exosomes contain specific miRNAs associated with a multi-protein complex known as RNA-induced silencing complex (RISC).
In addition to RISC, the breast cancer exosomes also house Dicer and two other proteins, AGO2 and TRBP, all of which together provoke tumor growth.
“The role of miRNAs associated with exosomes in cancer progression is largely unknown. Many studies have suggested the presence of miRNAs in exosomes and speculated on their function,” said Kalluri. “We demonstrated that inhibiting the action of Dicer in cancer exosomes significantly impairs tumor growth, raising the possibility that miRNAs in exosomes contributes to cancer progression.”
Kalluri’s study indicated that the interplay between Dicer and its “host” exosome may allow cancer cells to develop an “oncogenic field effect” by manipulating surrounding cells via exosomes. Think of a child blowing a dying dandelion’s spores into the wind where they float over a newly mowed lawn and one can envision how this molecular mixer easily spreads the disease to surrounding tissue.
“这些研究反映需要评估的miRNA机械的外来体的功能作用及其在肿瘤进展和转移的作用，”卡鲁说。
卡鲁的MD安德森的团队成员包括索尼娅·梅洛和ル杉本，无论是在癌症生物学博士后;安东尼卢奇，医学博士，外科肿瘤学教授;克里斯蒂娜·伊万，妇科肿瘤;和乔治·克林，实验治疗的医学博士，博士，教授。其他合作机构包括贝斯以色列女执事医疗中心和哈佛医学院波士顿;Bellvitge生物医学研究所，巴塞罗那188bet体育网址，西班牙;荷兰癌症研究所，荷兰阿姆斯特丹;和神经科学中心和细胞生物学，葡萄牙科英布拉。
这项研究是主要由癌症Preve资助ntion and Research Institute of Texas. The authors are also supported by the National Science Foundation (EFRI-1240410, CBET-0922876 and CBET-1144025), the National Institutes of Health/National Cancer Institute (R01 EB003472, R01 EB006462, 1UH2TR00943-01, 1R01 CA182905-01, CA-163191, CA155370, CA 151925, DK 081576, and DK 055001), The National Cancer Institute (the Human Frontiers Science Program, the Alan M. Gewirtz Leukemia & Lymphoma Society, the MD Anders Research Trust, The University of Texas System Regents Health Research Scholarship program, and the CCL Global Research Foundation.