Structure and function analysis in circulating tumor cells: using nanotechnology to study nuclear size in prostate cancer

American Journal of Clinical and Experimental Urology

Shirley Cheng¹  Lel²  Jie-Fu Chen³  Yu-Jen Jan⁴  Nu Yao⁵ 

[1] Cancer Biology Program, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048, USA;Department of Molecular and Medical Pharmacology, University of California, Los Angeles, USA;Division Of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA;Translational Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048, USA;Urologic Oncology Program Uro-Oncology Laboratories, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048, USA

关键词: Circulating tumor cells;    nuclear size;    visceral metastases;    prostate cancer;    NanoVelcro;    biomarkers;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Professor Donald Coffey and his laboratory pioneered studies showing the relationships between nuclear shape and cellular function. In doing so, he and his students established the field of nuclear morphometry in prostate cancer. By using perioperative tissues via biopsies and surgical sampling, Dr. Coffey’s team discovered that nuclear shape and other pathologic features correlated with clinical outcome measures. Cancer cells also exist outside of solid tumor masses as they can be shed from both primary and metastatic lesions into the circulatory system. The pool of these circulating tumor cells (CTCs) is heterogeneous. While some of these CTCs are passively shed into the circulation, others are active metastasizers with invasive potential. Advances in nanotechnology now make it possible to study morphologic features such as nuclear shape of CTCs in the bloodstream via liquid biopsy. Compared to traditional tissue sampling, liquid biopsy allows for minimally invasive, repetitive, and systemic disease sampling, which overcomes disease misrepresentation issues due to tumor temporospatial heterogeneity. Our team developed a novel liquid biopsy approach, the NanoVelcro assay, which allows us to identify morphologic heterogeneity in the CTC compartment. By applying classical methods of nuclear morphometry, we identified very small nuclear CTCs (vsnCTCs) in prostate cancer patients. Our initial studies showed that vsnCTCs strongly correlated with unfavorable clinical behaviors including the disposition to visceral metastases. These approaches may continue to yield additional insights into dynamic clinical behaviors, which creates an opportunity for more comprehensive and accurate cancer profiling. Ultimately, these advancements will allow physicians to employ more accurate and personalized treatments, helping the field reach the goal of true precision medicine.

【 授权许可】

CC BY-NC