Trop-2-Cells, Their Exosomal Cargo, and the Potential Impact on Diagnostics and Therapeutics in Breast Cancer: The Expanding Frontiers

Abstract

breast, ovary, and endometrium. 3,4 Appar-ently, this Trop-2 gene upregulation provides selective advantages for Trop-2 overexpressing cancer cells. Although further research would be needed to provide more evidence, Trop-2 gene overexpression would correlate with the abundance of the Trop-2 protein on the cell membrane and inside the cytoplasm, which could be detected using immunohistochemical staining of a pathological slide. 5,6 Trop-2 glycoproteins are involved in the cancer cell-cell as well as cell-extracellular matrix communications. As a result, cancer cells could migrate and possess invasive properties within the tumor microenvironment. Furthermore, research in this arena in the past decade has provided some crucial insights that Trop2 plays a central role in the cleavage by tissue necrosis factor-α-converting enzyme (TACE, also known as ADAM17) and activating Beta-1 (β 1 ) integrin-dependent migration through extracellular fibronectin of which the main receptors are primarily Alpha 5 beta 1 (α 5 β 1 ) integrins assembling with the intracellular focal adhesion kinase. 7–10 This cascade of interactions and activations would ul-Trop-2-Cells, Abstract Recently, an anti-trophoblast surface antigen-2 (Trop-2) antibody-drug conjugate targeting Trop-2 positive cancer cells has been approved for treating patients with unresectable locally advanced or metastatic triple-negative breast cancer, who have failed two or more lines of systemic chemotherapy. This has renewed the interest in translational research of Trop-2 positive breast cancer, the gene TACSTD2 and microRNAs that interact with it, and the signaling networks sparked by Trop-2 mediated signaling. In addi-tion, this opinion paper argues that exosomes, extracellular vesicles that are released from Trop-2 positive cancer cells, could play a significant role in cancer progression. Furthermore, diagnostic applications using Trop-2-released exosomes, the cargo exosomes carry, which could be any genetic information such as specific miRNAs, adhesion molecules such as integrins, and metabolites, are yet to be explored in breast cancer patients. Most of the evidence and data are obtained from studies in epithelial cancers other than breast cancers, which have been introduced in the current paper. Therefore, this article briefly summarizes previously published data on other cancer types, forms some hypotheses, and proposes research questions and directions that may be explored further.