Optimization of endometrial cancer organoids establishment by cancer-associated fibroblasts

Abstract

Most endometrial cancers (EC) are diagnosed at an early stage with a favorable prognosis. However, for patients with advanced or recurrent disease, the chemotherapy response rate and overall survival remain poor. A novel in vitro model, tumor organoids, has important value in providing a more individualized treatment plan for tumor patients. However, the slow growth of the established EC organoid seriously hinders the application of EC organoids. Cancer-associated fibroblasts (CAFs), the main component of tumor stroma, have been reported to promote the proliferation of endometrial cancer cell lines and primary endometrial cancer cells in vivo and in vitro. Therefore, we optimized the current endometrial cancer organoid by introducing CAFs isolated from EC lesions. Here we developed long-term expandable organoids from endometrial cancer lesions, which show disease-associated traits and cancer-linked mutations. Based on the co-culture of CAFs and endometrial cancer organoids, we found that CAFs could promote the growth of endometrial cancer organoids, might by secreting factors according to the result that CAFs could also promote the growth. Our research provided a more promising model for the basic and preclinical study of endometrial cancer. Key words: endometrial cancer; organoids; cancer-associated fibroblasts; optimization Endometrial cancer (EC) is the sixth most common female cancer worldwide and the fourth most common in high-income countries [1]. The incidence of EC has risen by 57% since the early 1990s in some populations [1]. There are two types of endometrial cancer: type I EC is estrogen-dependent with a favorable prognosis (85% 5-years survival rate); type II EC is

Research progress on the application of organoids in gynecological tumors

“…Another study has found that removing N2 from the culture medium and adding ROCK inhibitors can promote long-term expansion and cryopreservation of organoids ( Berg et al, 2021 ). Wu et al optimized the current EC-like organs by introducing CAFs isolated from EC lesions ( Wu et al, 2022 ). Based on co-cultivation of CAFs and EC-like organs, they found that CAFs can promote the growth of EC-like organs, possibly by secreting factors.…”

“…However, the specific experimental conditions reported in each study are different and have been specifically listed above. Wu et al optimized the current EC like organs by introducing cancer-associated fibroblasts (CAFs) isolated from EC lesions ( Wu et al, 2022 ). Based on co-cultivation of CAFs and EC-like organs, they found that CAFs can promote the growth of EC-like organs, possibly by secreting factors.…”

“…Based on co-cultivation of CAFs and EC-like organs, they found that CAFs can promote the growth of EC-like organs, possibly by secreting factors. According to the results, CAFs can also promote growth, providing a more promising model for the basic and preclinical research of EC ( Wu et al, 2022 ).…”

Revolutionizing the female reproductive system research using microfluidic chip platform

“…Mostly, in vitro studies on endometrial cancer are based on organoid models. By introducing fibroblasts isolated from endometrial cancer lesions to optimize the current endometrial cancer organoids, the disease-related characteristics and cancer-related mutations were studied [ 275 ]. Organoids faithfully reproduce the genotype of the disease, which will be valuable for exploring the proliferative phenotype and the molecular mechanism of cancer development [ 276 ].…”

Review on Advanced Cancer Modeling for a Cancer Study

“…Given that the characteristics of tumor organoids derived from cancer patients faithfully recapitulate the architecture of their original tumor tissues and organoids, cancer-organoid-culture technology has expanded to other types of cancers. Many researchers have established long-term organoid cultures by using primary-colon [ 15 , 44 ], lung [ 45 , 46 , 47 ], esophageal [ 48 ], pancreatic [ 49 , 50 , 51 ], prostate [ 51 , 52 , 53 ], breast [ 30 , 54 , 55 ], stomach [ 56 , 57 ], liver [ 40 , 58 ], and endometrial [ 59 , 60 ] cancer and normal tissues.…”