**Acknowledgements**

**4. Other mechanism of dissemination**

thought.

52 Tumor Metastasis

**5. Conclusion**

This enables some cancer cells to enter into the blood circulation.

While the transcoelomic route of peritoneal dissemination is thought to be the predominant mode of ovarian cancer spread, other mechanisms do exist. The ascites produced in the peritoneal cavity is typically drained through the lymph vessels present in the diaphragm [36]. This provides the cancer cells present in the ascites, the opportunity to metastasize to the lymph nodes. Moreover, the lymphatic vessels drain into the left subclavian vein via the thoracic duct.

Although circulating ovarian cancer cells have long been reported to be present in the blood [52], it has typically been considered a mode of dissemination only in the very late stages of the disease. The prevalent reasoning being that although the ovarian cancer cells enter into the circulation, they are not yet adept at surviving in the circulation and establish metastatic tumors in a very different 'soil.' However, recent reports have suggested that hematogenous metastasis may be more commonly occurring in ovarian cancer that we had thought [16, 53]. Using a parabiosis model, Pradeep et al. have very elegantly demonstrated the haematogenous metastasis of the ovarian cancer cells from the primary tumor in one mouse to the omentum of the paired mouse [16]. The expression of ErBB3 in the ovarian cancer cells entering into circulation and the omental expression of NRG1 was found to be the key players responsible for the hematogenous metastasis [16]. Interestingly, the use of mouse models of hematogenous ovarian cancer metastasis revealed a preferential homing of the cancer cells to the ovary followed by the development of ascites and subsequent peritoneal metastasis [53]. When the ovaries were removed before injecting the cancer cells, peritoneal metastasis and ascites formation were completely abolished [53]. Taken together, recent evidences point toward a more significant role of hematogenous dissemination in ovarian cancer that previously

Ovarian cancer is a malignancy where most patients are treated for metastatic disease because they are usually diagnosed at an advanced stage. A better understanding of the process of metastasis and the underlying mechanisms of regulation is crucial for development of effective therapies. However, our knowledge in this field remains limited. It has become increasingly clear that there are multiple different ways in which the cancer cells disseminate, and the transcoelomic rout remains the most predominant mode. While it appears to be a relatively simpler way to metastasize, the steps involved pose their own unique challenges to the cancer cells. Moreover, the absence of the need for invasion, intravasation, and extravasation can potentially enable the cancer cells to metastasize earlier and in greater numbers than in case of hematogenous metastasis. Studying the underlying mechanisms have remained challenging but the evolution of *in vitro* organotypic 3D culture models have opened up opportunities to conduct more meaningful experiments and have lead to significant leaps in knowledge [6, 24, 45]. Use of ovarian cancer cell lines that closely resemble the mutational profile of clinical A Department of Defense Ovarian Cancer Academy Award supported AKM.
