Background: Epithelial ovarian cancer is one of the most malignant cancers in women because metastasis occurs in the most of patients by the time of diagnosis. Cancer cells have strong capacity to form angiogenesis or vasculogenic mimicry, which plays the major role in its malignant phenotype. Vasculogenic mimicry might contribute to the failure of the angiogenesis-targeted therapy strategies. Under the microenvironment of the tumor, hypoxia is the most common phenomena because of the vast energy and oxygen consuming. In the present study, the endothelial-like cells induced by hypoxia from SKOV-3 and ES-2 ovarian cancer cells were harvested to investigate the changes in their biological behaviors.Methods: The endothelial-like cells from SKOV-3 and ES-2 cells were harvested by laser capture microdissection. The biological behaviors of the endothelial-like cells, including proliferation, cell cycle, apoptosis, invasion and telomerase activity were determined by MTT, FCM, Transwell chamber and TRAP-ELISA methods. HIF-1α is the most important factor for the behavior changes under hypoxic condition. Some other genes relative to biological behaviors are also changes following the changes of HIF-1α. In order to elucidate the underlying mechanisms for these changes by hypoxia, the relative genes expressions including HIF-1α, CyclinD1, Flk-1, VEGF, p53 and V-src were determined by real-time PCR.Results: SKOV-3 and ES-2 cells were resistant to hypoxia by adoption of proliferation, apoptosis, differentiation and invasion. Combined with other studies, the more poorly cancer cells differentiate, the more strongly cells are resistant to hypoxia, the more possible to form vasculogenic mimicry. The changes in the expression of HIF-1α, and HIF-1α-dependent VEGF, Flk-1, Cyclin D1, and HIF-1α-independent p53 have been involved in this process.Conclusions: HIF-1α took an important role in the behavioral changes of SKOV-3 and ES-2 cells by hypoxia. At the same time, other mechanisms were also involved in this process.

CA125 is a prevalently used serum biomarker for detecting ovarian cancer over the last three decades. However, it has a significant deficiency in screening for early-stage cancer. With the purpose of exploring an effective approach to improve its performance in early diagnosis, we investigated the postprandial fluctuation pattern of cancer-derived CA125 and the underlying mechanism. In two medical centers, 551 patients sonographically diagnosed with ovarian (adnexal) cysts (< 5 cm in diameter) were enrolled and divided into five disease groups (pelvic inflammatory cysts, retention cysts, endometrioma, benign/borderline cystadenoma and malignant cysts). The subtle differences in 1-h postprandial serum CA125 increases were compared between disease groups. A support vector machine (SVM)-based algorithm was used for refining the performance of CA125 postprandial increment. Ovarian cancer xenograft animal and cancer cell models were used to recapitulate the clinical findings and reveal the molecular basis of postprandial blood glucose and insulin in invoking the synthesis/secretion/re-absorption of CA125. Patients with ovarian cancer presented the highest postprandial increment 13.3 ± 0.7% (mean ± standard deviation) among the five disease groups. Using a CA125 increment ≥ 10% criterion, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) reached 83.3, 96.3, 61.1 and 98.8%, respectively, for early-stage ovarian cancer. This performance was further improved by the SVM-based CA125-increment algorithm, which exhibited 91.7% sensitivity, 99.2% specificity, 89.2% PPV and 99.4% NPV. Both modalities manifested diagnostic advantages over the traditional CA125 test (75.0% sensitivity, 25.4% specificity, 6.6% PPV and 93.6% NPV at the cut-off of 35 U/mL). Regarding the molecular basis, the postprandial blood glucose and insulin-invoked overexpression of Mucin 16 (encoding CA125) were demonstrated in animal and cancer cell models, which were mediated by the PI3K-Akt pathway. Nevertheless, a Mesothelin-based CA125 re-absorption behavior was noted in the treated cancer cells, which contributed to the over-drop following the postprandial peak of serum CA125. Cancer-derived serum CA125 possesses a unique and distinctive postprandial pattern, that distinguishes it from the common CA125 elevation in a benign disease condition. The dynamic measurement/assessment strategy can achieve a discriminatory power superior to that of a static test.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

The initiation and progression of cancer depend on the genetic alterations inherent in cancer cells, coupled with the mutual interplay of cancer cells with the surrounding tumor stroma. The platelet-derived growth factor (PDGF) family, as a mesenchymal growth factor, was involved in tumor progression by affecting the surrounding tumor stroma in some cancer types. However, the association of the PDGF family with the ovarian cancer stroma remains elusive. In our study, we first explored the expression pattern of the PDGF family using RNA expression profiles from public databases. We found that the PDGF family was highly expressed in tumor stroma compared with the corresponding epithelial components of ovarian cancer. In particular, PDGF receptors were weakly expressed in ovarian cancer tissues compared with the respective normal tissues; even in tumor mass, PDGF receptors were predominantly expressed by tumor stroma rather than ovarian cancer cells. Importantly, functional enrichment analyses and correlation analyses revealed that the PDGF family was strongly associated with activated stromal scores in ovarian cancer, including higher stromal scores, enriched pathways related to the extracellular matrix (ECM) organization and remodeling, elevated cancer-associated fibroblasts (CAFs) infiltration, and increased tumor-associated macrophages (TAMs) infiltration, especially macrophage M2. Besides, the positive correlations of the PDGF family with CAFs infiltration and macrophage M2 infiltration were observed in other various cancer types. Of note, the PDGF family was also involved in tumor progression-related pathways, such as transforming growth factor β (TGF-β) signaling, epithelial-mesenchymal transition (EMT), angiogenesis, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling. Higher expressions of PDGF receptors were also observed in ovarian cancer patients with venous or lymphatic invasion. Furthermore, we uncovered the prognostic prediction of the PDGF family in ovarian cancer and constructed a PDGF family-based risk prognosis model with a hazard ratio of 1.932 ( ) and value < 0.01 ( , 0.752 for 1 year and 2 years, respectively). Taken together, we demonstrated that ovarian cancers with high PDGF family expression biologically exhibit malignant progression behaviors as well as poor clinical survival, which is attributed to the activated tumor stroma in ovarian cancer.