Cell fusion promotes chemoresistance in metastatic colon carcinoma

Abstract

Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investigated the role of these proteins namely tetraspanin CD81/CD9, ADAM10, GTP-binding protein a13, radixin, myosin regulatory light chain and RhoA in the regulation of colon cancer cell fusion. We also found a previously unrecognized role of ADAM10, Ga13 and RhoA in promoting cell fusion. Finally, we show that the occurrence of cell fusion in a metastatic model of colon carcinoma causes the appearance of cells resistant to both 5-fluorouracil and oxaliplatin. These findings highlight the importance of cell fusion in cancer progression and raise significant implications for overcoming chemoresistance in metastatic colon cancer.

A disintegrin and metalloprotease (ADAM)10 is highly expressed in hepatocellular carcinoma and is associated with tumour progression

“…27 Carloni et al showed that ADAM10 contributes to cancer cell fusion. 28 In the current study, our data showed that at the mRNA and protein level, ADAM10 was significantly upregulated in HCC compared with adjacent normal tissue. This suggests that ADAM10 has diagnostic value.…”

Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery

“…Growing in vitro (Busund et al 2002, 2003; Shabo et al 2015; Wei et al 2014), in vivo (Powell et al 2011; Silk et al 2013), and clinical (LaBerge et al 2017; Lazova et al 2013; Yilmaz et al 2005) data indicate that this process occurs in solid tumors and may play a significant role in clinical tumor progression. Moreover, this process generates malignant cell clones (hybrids) with reduced susceptibility to oncological treatments (Carloni et al 2013; Nagler et al 2011; Wang et al 2012; Yang et al 2010). …”

Polymer Nanoassemblies With solvato- and halo-fluorochromism for Drug Release Monitoring and Metastasis Imaging

“…Real-time monitoring of the ADME of drugs in the body is expected to provide timely, personalized regimens during the course of treatment while maximizing accumulation of anticancer drugs in metastatic tumors [12]. However, even if a sufficient amount of anticancer drugs are delivered to metastatic tumors, not all drugs are effective at killing cancer cells in micrometastatic colonies [13]. Metastatic tumor cells that grow quickly produce a large amount of acidic byproducts, such as lactic acid, during the conversion of glucose into energy [14].…”