A Different Exosome Secretion Pattern Characterizes Patient-Derived Colorectal Cancer Multicellular Spheroids and Their Mouse Xenografts
Michela Relucenti,
Federica Francescangeli,
Maria Laura De Angelis,
Vito D’Andrea,
Selenia Miglietta,
Orlando Donfrancesco,
Xiaobo Li,
Rui Chen,
Ann Zeuner,
Giuseppe Familiari
Affiliations
Michela Relucenti
Section of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy
Federica Francescangeli
Department of Oncology and Molecular Medicine, National Institute of Health (Istituto Superiore di Sanità), 00161 Rome, Italy
Maria Laura De Angelis
Department of Oncology and Molecular Medicine, National Institute of Health (Istituto Superiore di Sanità), 00161 Rome, Italy
Vito D’Andrea
Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy
Selenia Miglietta
Section of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy
Orlando Donfrancesco
Section of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy
Xiaobo Li
Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Rui Chen
Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Ann Zeuner
Department of Oncology and Molecular Medicine, National Institute of Health (Istituto Superiore di Sanità), 00161 Rome, Italy
Giuseppe Familiari
Section of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy
Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage responsible for CRC and its metastatic behavior and responsiveness to therapy are needed. Exosomes’ role in tumorigenesis and the metastatic process was demonstrated, and the material content and size of the exosomes are associated with a poor prognosis of CRC. Exosomes are generally imagined after their recovery from blood serum as isolated entities, and our work aims to investigate them “in situ” in their native environment by scanning and transmission electron microscopy to understand their secretion modalities. We studied CRC stem cells in patient-derived multicellular tumor spheroids (MTSs) and in their mouse xenograft to find possible differences in terms of exosome amount, size, and secretion site between in vitro and in vivo models. We observed that MTSs’ exosome secretion patterns depend on their structural complexity: few-layer MTSs show a lesser exosome secretion, limited to the apical domain of cancer cells, secretion increases in multilayered MTSs, and it develops from apical and basolateral cancer cells domains. In xenograft models, exosome secretion occurs from all cancer cell domains, and it is quantitatively greater than that observed in MTSs. This difference in exosome secretion pattern between MTSs and xenografts may be due to the influence of surrounding non-tumor cells.
