The study results showed that increased expression of MMP-12 was associated with tumor progression in gastric cancer. It also provided the first evidence for MMP-12 expression in gastric cancer as an independent prognostic factor.

Introduction. This study was aimed at exploring whether the Golgi membrane protein 1 (GOLM1) enhanced ovarian cancer metastasis through B7-H3-dependent way. Methods. We collected the ovarian cancer patient samples from available databases including GEPIA, starBase, and Protein Altas that have GOLM1 and B7-H3 mRNA and protein expression. Ovarian cancer cell line SKOV3 was purchased. Knockdown GOLM1 and B7-H3 cell lines were obtained through introducing shRNAs by lentivirus package system, while GOLM1 or B7-H3 overexpression cell line was obtained by introducing GOLM1 full-length gene. Furthermore, wound-healing assay and Transwell assay were performed to assess tumor invasion and metastasis abilities; related proteins’ expression was quantitated by western blotting, ELISA, and flow cytometry assay. The protein interaction was quantified by co-immunoprecipitation. Results. GOLM1 has the correlative expression pattern with B7-H3 in ovarian cancer through patient sample databases (R = 0.421). GOLM1 knockdown had minimal impact on B7-H3 mRNA synthesis, while downregulated B7-H3 protein expression on tumor membrane and soluble B7-H3 (sB7-H3) level ( p < 0.05 ) through physical interaction, GOLM1 knockdown, significantly reduce tumor invasion and metastasis in vitro ( p < 0.05 ). Moreover, exogenous sB7-H3 significantly rescued this inhibitory effect. Both GOLM1 and B7-H3 knockdown restrained tumor growth and metastasis in immunodeficient mice and prolonged the survival rate. Conclusions. GOLM1 acts as an initial oncogenic driving gene by promoting ovarian cancer invasion and metastasis through modulating B7-H3 protein maturation and secretion.

Potent CAR-T therapies that target appropriate antigens can benefit the treatment of anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL), which is the most common subtype of T cell lymphoma. In this study, we observed overexpression of B7-H3 in ALCL cell lines derived from clinical samples and differential expression of B7-H3 in an ALK-induced T cell transformation model. A B7-H3-redirected CAR based on scFv from mAb 376.96 was developed. B7-H3 CAR-T cells showed strong cytotoxicity and cytokine secretion against target ALCL cells (SUP-M2, SU-DHL-1, and Karpas 299) in vitro. Furthermore, the B7-H3 CAR-T cells exhibited proliferative capacity and a memory phenotype upon repeated antigen stimulation. We demonstrated that B7-H3 CAR-T cells could promptly eradicate ALCL in murine xenografts. Taken together, B7-H3 is a novel and promising target in ALCLs and B7-H3 CAR-T may be a viable treatment option for ALCL.

<b><i>Backgrounds:</i></b> Exosomes from multiple sources function as regulatory factors in progression of various tumors. However, studies on the impact of exosomes from cancer-associated fibroblasts (CAFs) on tumor-cell proliferation, migration, invasion, and cycle regulation in clear-cell renal-cell carcinoma (ccRCC) are still lacking. <b><i>Methods:</i></b> A Western blot assay was performed to test the exosome-related marker protein level in exosomes derived from CAFs and normal fibroblasts (NFs). A confocal microscope was utilized to observe the internalization of CAF- and NF-derived exosomes after coculturing with cancer cells. MTT, EdU, colony formation, and transwell assays were conducted to detect progression of cancer cells incubated with CAF-derived exosomes. A Western blot assay was also conducted to test expression levels of metastasis-associated proteins. Changes in cell apoptosis and cell cycle were measured by flow cytometry. <b><i>Results:</i></b> Expression of CAF-derived exosome-related marker proteins was higher than that from NFs. Exosomes derived from CAFs and NFs could enter into cancer cells smoothly and be internalized by cancer cells. After cancer cells were cocultured with CAF-derived exosomes, cell proliferation, migration, and invasion were notably enhanced, and cell apoptosis was reduced. Moreover, expression of fibronectin, N-cadherin, vimentin, MMP9, and MMP2 in cancer cells increased, while E-cadherin was decreased. Besides, the proportion of cancer cells in the S phase increased. <b><i>Conclusion:</i></b> CAF-derived exosomes are internalized into ccRCC cells and promote the progression of ccRCC.

Background: Ovarian cancer (OC) is a globally malignant gynecological disease with aggressive nature, most OC cases are diagnosed at late stages and the 5-year overall survival was less than 35% after conventional treatment. Furthermore, OC patients are rarely responsive to immune-check-point inhibitor therapy, and the efficacy of CAR-T therapy was also modest due to inefficient T cell infiltration. Hence, additional approaches to improve T cell traffic in OC tumor sites need to be developed. Methods: In this report, based on the structure of the chimeric antigen receptor, we developed a novel adoptive T cell therapy with a ligand-receptor as the binding motif to improve CA125 targeting therapeutic effect against ovarian cancer. As mesothelin can naturally bind to CA125 with high affinity, the core-binding fragment of mesothelin was concatenated with 4-1BB and CD3ζ signal fragments to assemble a novel CA125-targeting chimeric receptor (CR). Meanwhile, the CAR structure targeting CA125 derived from the 4H11 antibody was also analogously constructed. CR and CAR coding RNA were electroporated into T cells to test their antitumor activity both in vitro and in vivo. Results: While CR-T or CAR-T has shown moderate activity targeting two ovarian cancer cell lines, CR and CAR co-expressed T cells had a superior killing effect than T cells expressing CR or CAR alone. Upon interaction with ovarian tumors, the activation markers and functional cytokine release abilities were also significantly increased in CR and CAR co-expressed T cells. Similarly, CR and CAR co-expressed T cells could persistently control transplanted ovarian cancer tumor growth in NOD/SCID mice and prolong the overall survival of tumor-challenged mice. Transcriptome sequencing showed that survival and cytotoxicity properties of CR and CAR co-expressed T cells were significantly altered compared with T cells expressing CR or CAR alone. Conclusion: Our work demonstrates that CA125 targeting CR and CAR can synergistically kill ovarian cancer, suggesting these two binding motifs simultaneously targeting CA125 on tumors may yield improved responses in ovarian cancer treatment.