The contractile protein MYH9 (non-muscle myosin IIA) is an actin-binding protein that plays a fundamental role in cell adhesion, migration, and division. However, its distinct role in colorectal cancer (CRC) still remains unidentified. In this study, we detected significant MYH9 overexpression in CRC samples compared with paired normal tissues using western blotting and tissue microarray immunohistochemistry (IHC). Moreover, analysis of patient clinical information demonstrated that MYH9 overexpression was strongly correlated with lymph node metastasis and poor overall survival. Endogenous overexpression of MYH9 enhanced the ability of cell proliferation and migration in vitro, and accelerated CRC growth in mouse models. Silencing of MYH9 revealed repressive effects on CRC cells in vitro and in vivo. Furthermore, primary biomechanics that involved MAPK/AKT signaling mediated epithelial-mesenchymal transition (EMT) was uncovered underlying MYH9 dependent cell behaviors. Collectively, our data showed that MYH9 significantly promoted tumorigenesis by regulating MAPK/AKT signaling, and was remarkably correlated with poor prognosis in CRC. MYH9 may thus be a novel biomarker and drug target in the diagnosis and treatment of CRC.

Dendritic cell (DC) based immunotherapy is a promising approach for cancer treatment and has been approved in clinical settings for decades. Clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC immunotherapy is strongly influenced by their ability to migrate to the draining lymph nodes (LNs). Therefore, it is critical to deliver DCs and monitor the in vivo biodistributions of DCs after administration. The purpose of this study is to determine whether a novel injection route of DCs improves DC migration to LNs, tissues, organs and lymphatics. In the present study, a modified method was investigated to acquire DCs from mouse bone marrow. Cultured antibody labeled DCs were analyzed by flow cytometry. India ink was used to visualize mouse abdominal LNs and PKH26 was utilized to label DCs for intraperitoneal (IP) injection, results were evaluated by histology. Our results showed that large amounts of DCs with a relatively high purity were acquired. IP injection of india ink marked the abdominal LNs and PKH26 labeled DCs showed IP was an effective administration route to increase the absorption of viable DCs, and different time points after IP inject showed no significant difference of the migrated DCs. The findings indicated that large amounts of high purity DCs can be acquired through our method and IP injection accelerates DCs migration to abdominal LNs, which can be directly translated to clinical settings, especially for abdominal cancers. This study makes a foundation for future researches of DC-based immunotherapy as a treatment modality against cancer.

In recent decades, immunotherapy has undergone extensive developments for oncologic therapy applications. Dendritic cells (DCs) plays a fundamental role in cell-based vaccination immunotherapy against various types of cancer. It involves stimulating innate and adaptive immunity, in particular cytotoxic T-cell mediated antitumor effects, against targeted tumors and has been studied in both preclinical and clinical settings. Nevertheless, clinical outcomes have been unsatisfying. The antitumor response requires sufficient migration of viable DCs from primary administration site to targeted tumors through related lymphatics. The dynamics and mechanisms of the DCs migration still need further investigation. Here, we briefly introduce the current clinically applicable methods for manufacturing DC-based cancer vaccines and their most commonly used non-invasive, real-time tracking approaches. Furthermore, we propose a hypothesis that intraperitoneal injection may improve the efficiency of DC-based cancer vaccine.