A different exosome secretion pattern characterizes patient-derived colorectal cancer multicellular spheroids and their mouse xenografts

Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancerlineage 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 materialcontent and size of the exosomes are associated with a poor prognosis of CRC. Exosomes are generallyimagined after their recovery from blood serum as isolated entities, and our work aims toinvestigate them “in situ” in their native environment by scanning and transmission electron microscopyto understand their secretion modalities. We studied CRC stem cells in patient-derivedmulticellular tumor spheroids (MTSs) and in their mouse xenograft to find possible differences interms of exosome amount, size, and secretion site between in vitro and in vivo models. We observedthat MTSs’ exosome secretion patterns depend on their structural complexity: few-layer MTSs showa lesser exosome secretion, limited to the apical domain of cancer cells, secretion increases in multilayeredMTSs, 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 thatobserved in MTSs. This difference in exosome secretion pattern between MTSs and xenografts maybe due to the influence of surrounding non-tumor cells.