Abstract
Through lateral transfer, extra-cellular vesicles (EVs) transport their DNA, miRNA, mRNA and proteins such as enzymes mediating drug resistance, transporters as well as growth factors to neighboring cells. By virtue of this horizontal transfer, EVs potentially regulate cell growth, migration, angiogenesis and metastasis and increase tissue permeability in cancer. Furthermore, EVs regulate immune factors and allow the tumor cells to evade immune recognition and cell death. To explore if the proteomes of exosomes support functional transfer of cancer hallmarks, in this meta-analysis, we compared EVs and whole cell proteomes from the NCI-60 human tumor cell line panel. We observed a subgroup of proteins in each cancer hallmark signature as highly abundant and consistently expressed in EVs from all cell lines. Among these were oncoproteins frequently targeted in cancer therapies whose presence on EVs could potentially render therapies less effective by serving as decoys.
Highlights
Carcinogenesis involves sequential steps including early steps of gene mutations that lead to genome instability and increased growth
Caveats include the fact that this picture might change when more cancer cell lines are included and that liquid biopsies from patients contains extra-cellular vesicles (EVs) from stromal and immune cells, which could obscure the specificity in predicting tissue of origin of primary tumor
We investigate which receptor tyrosine kinases (RTKs) are abundant in the EVs derived from the NCI 60 cell lines (Figure 6)
Summary
Carcinogenesis involves sequential steps including early steps of gene mutations that lead to genome instability and increased growth. Cancer research has provided evidence that tumor development is a multi-step process in the transformation of a normal cell into a malignant derivative This process was comprehensively schematized, by Hanahan and Weinberg, into six acquired capabilities of cancer cells, constituting the well-established hallmarks of cancer [2]: 1. A substantial body of evidence drove the authors to pinpoint new capabilities as emerging hallmarks of cancer These capabilities relate to the involvement of the immune system as a perpetuator of an inflammatory environment before tumor development and during its establishment. To draw comparisons between the proteome of cancer cells and derived tumor microvesicles, the present study addresses four of the six proposed hallmarks of cancer [2], namely sustaining proliferative signaling, resisting cell death, inducing angiogenesis and activating invasion and metastasis. We argue that the large data sets provided by Hurwitz et al [22] contain adequate information to justify a complementary analysis
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