Tumour-associated circulating microparticles: a novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia

Abstract

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the socalled liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM Oncotarget 30868 www.impactjournals.com/oncotarget apoptosis and that are released into the extracellular space. MPs can be isolated from human fluids such as whole blood, plasma, serum or e.g. synovial fluid [1][2][3][4][5][6]. They carry the surface signature of their cell of origin and the quantification of MP subsets using FACS sorting permits a non-invasive assessment of cell specific pathologies, especially in inflammation [7][8][9][10]. MPs have to be differentiated and separated from exosomes, which are derived from intracellular vesicles and do not carry cell surface markers of their origin, and from the larger fragments of apoptotic bodies [2,3]. So far, only a few and technically limited studies have been performed on putative cancer-derived MPs or microvesicles identified by single surface marker [11][12][13]. Therefore, we explored the diagnostic potential of tumour-associated MPs (taMPs) and MP subtypes in thoroughly characterised patients with various underlying cancer entities such as colorectal carcinoma, non-small cell lung carcinoma and pancreas carcinoma. RESULTS Patients with CRC, other neoplasia or thyroid nodules (struma nodosa) show characteristic MP profilesBased on literature research various cancer markers were considered for the detection of taMPs expressing common cancer antigens as EpCAM and CD147. Corresponding cancer lines were screened for the chosen surface antigens (data not shown). Indeed, EpCAM and CD147 were identified on the surface of cancer cell lines of colorectal (CRC), lung (NSCLC) and pancreas (PaCa) (data not shown). MPs were isolated by differential centrifugation of sera of total 103 confirmed cancer patients. Median EpCAM + taMPs values were significantly elevated (oneway ANOVA) in patients with CRC (n = 52), NSCLC (n = 40), PaCa (n = 11) by an average of 2.3 fold irrespective of the tumour entity and size ( Figure 1A and Table 1). Surprisingly, EpCAM + taMPs were also found elevated in thyroid nodules patients (short: struma, n = 40) as compared to healthy controls by 1.9 fold (p < 0.05). Nevertheless, the antigen combination of EpC...

Increased levels of circulating platelet‐derived microparticles are associated with metastatic cutaneous melanoma

“…Although PMPs level has been correlated with metastatic tumors, [2,4] the function of high PMPs levels in advanced melanoma still need to be explored. Our study demonstrates that circulating PMPs are …”

“…We do not have any clear explanation but we may hypothesise that PMPs reflect the tumor microenvironment, including angiogenesis, inflammatory reaction and antitumoral immunity rather than tumor burden. [5] It may also be suggested that PMPs may not be representative of tumor burden as recently suggested by Willms et al [4] Cancer-associated venous thromboembolism constitutes the second cause of death after cancer. [7] We previously observed an inverse correlation between PMPs and clotting times with a lower clotting time in stage IV patients as compared to stage III patients.…”

Performance of different biomarkers for the management of hepatocellular carcinoma

“…In addition, EpCAM+CD147+ taMPs were significantly correlating with CRC tumor volume (r = 0.7288, P < 0.0001). Furthermore, EpCAM+ taMPs were found decreased after tumor resection in serum of CRC patients suggesting a close dependence with tumor presence [134] . They conclude that EpCAM+ and EpCAM+CD147+ taMPs might serve as an early indicator of cancer growth and monitor successful anti-tumour therapy and might be used as important liquid biopsy tool to differentiate between therapy responders and non-responders [134] .…”

“…Something that we have to be in account is that exosomes do not carry cell surface markers of their origin cells however MPs carry the surface signature of their cell of origin and the quantification of MP subsets using FACS sorting allows a non-invasive assessment of cell specific pathologies. Nowadays, there are many studies which focus is to identify the most efficient surface markers of tumor associated MPs (taMPs) and liver disease [134][135][136] .…”

Clinical significance of circulating microparticles in Ph− myeloproliferative neoplasms

“…MPs are considered to be biomarkers indicating the procoagulant state associated with a host of clinical diseases, including cancer, cardiovascular disease, sepsis and diabetes. Numerous studies have shown that the levels of circulating MPs are elevated in cancer patients, and that MPs contribute to the development of thrombosis-associated complications (9)(10)(11). MPs trigger blood coagulation and are expressed by numerous types of cancer cells (8).…”