Abstract
BackgroundWe have previously reported the formation of polyploid giant cancer cells (PGCCs) through endoreduplication or cell fusion after cobalt chloride (CoCl2) induction. Cell fusion plays an important role in development and disease. However, the underlying molecular mechanism concerning cell fusion in PGCCs formation and clinicopathological significances remains unclear.MethodsWe treat HCT116 and LoVo cell with CoCl2 and observed the cell fusion via fluorescent markers of different colors. Western blot and immunocytochemical staining were used to compare the expression and subcellular location of the fusion‐related proteins syncytin 1, CD9, and CD47 along with PKA RIα, JNK1, and c‐Jun between PGCCs and control cells from the HCT116 and LoVo cell lines. Moreover, 173 cases of colorectal tumor tissue samples were analyzed, including 47 cases of well‐differentiated primary colorectal cancer (group I) and 5 cases of corresponding metastatic tumors (group II), 38 cases of moderately differentiated primary colorectal cancer (group III) and 14 cases of corresponding metastatic tumors (group IV), and 42 cases of poorly differentiated primary colorectal cancer (group V) and 27 cases of corresponding metastatic tumors (group VI).ResultsThe expression of syncytin 1, CD9, and CD47 is higher in PGCCs than in control cells and they are located in the cytoplasm. The expression of PKA RIα and JNK1 decreased, and that of c‐Jun increased in PGCCs. The syncytin 1 expression was significantly different between groups I and II (P = 0.000), groups III and IV (P = 0.000), groups V and VI (P = 0.029), groups I and III (P = 0.001), groups III and V (P = 0.000), and groups I, III, and V (P = 0.000).ConclusionsThese data indicate that the cell fusion‐related proteins syncytin 1, CD9, and CD47 may be involved in PGCC formation, and that cAMP/PKA and JNK signaling is likely to promote PGCC formation via the regulation of cell fusion processes.
Highlights
Polyploid giant cancer cells (PGCCs) refer to a special subpopulation of cancer cells that were previously considered to be senescent cells without dividing ability or believed to be at the stage of mitotic catastrophe
We evaluated the subcellular location of syncytin 1, CD9, and CD47 with ICC staining, showing that these 3 fusion‐related proteins were expressed mainly in the cytoplasm in control cells and polyploid giant cancer cells (PGCCs) (Figure 2B), consistent with the western blotting results
We found that PKA RIα was expressed in the cytoplasm and nucleus in control cells and that cytoplasmic PKA RIα was highly expressed in PGCCs, while it was poorly expressed in the daughter cells (HCT116 and LoVo) (Figure 3C)
Summary
Polyploid giant cancer cells (PGCCs) refer to a special subpopulation of cancer cells that were previously considered to be senescent cells without dividing ability or believed to be at the stage of mitotic catastrophe. Recent studies have confirmed that PGCCs possess properties of cancer stem cells, with the expression of the cancer stem cell markers CD44 and CD133, and promote tumor maintenance and recurrence. These cells were identified to differentiate into benign tissues including adipose, cartilage, and bone tissues. It has recently been recognized that PGCCs contribute to the heterogeneity of solid tumors and that they are the most commonly described histological features in the pathologic diagnosis of tumors, with significant variation in nucleus shape and size Given that these features and functions of PGCCs have been shown, no specific conclusion for the mechanism of PGCC formation has yet been reached. Various signaling cascades such as the cAMP/PKA and JNK pathways have been shown to mediate the syncytialization process.[16,17] we assessed the expressional differences of PKA RIα, JNK1, and c‐Jun between the control cells and PGCCs
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