Fueling the Tumor Microenvironment with Cancer-Associated Adipocytes.

Despite their abundance throughout the body, adipocytes are often ignored for their contributions within the tumor microenvironment (TME). However, their role in fueling cancer is becoming increasingly apparent as interest in the TME has seen remarkable advances in recent years. A seminal study by Dirat and colleagues highlighted the essential impact of the peritumoral adipose tissue in breast cancer progression and was among the first to demonstrate that tumor cells can reprogram adipocytes within their immediate niche to adopt unique characteristics. These "cancer-associated adipocytes" (CAA) were found to exchange cytokines and lipids with tumor cells, leading to their metabolic rewiring and acquisition of proinflammatory and invasive phenotypes. These important discoveries have represented a breakthrough in understanding the bidirectional metabolic dialog between adipocytes and tumor cells, and have contributed renewed perspectives on the functional contributions of adipocytes within the TME. Moreover, the effects of CAA may be further amplified in the setting of obesity as lipids dramatically accumulate, providing insights into the link between breast cancer and its more advanced clinical state in obese conditions. Thus, the different molecular actors involved in the dialog between tumor cells and CAA represent promising therapeutic targets that may have particular relevance in improving prognosis in obese patients with cancer. See related article by Dirat and colleagues, Cancer Res 2011;71:2455-65.

A novel 3D culture model for human primary mammary adipocytes to study their metabolic crosstalk with breast cancer in lean and obese conditions.

Obesity is a negative prognosis factor for breast cancer. Yet, the biological mechanisms underlying this effect are still largely unknown. An emerging hypothesis is that the transfer of free fatty acids (FFA) between adipocytes and tumor cells might be altered under obese conditions, contributing to tumor progression. Currently there is a paucity of models to study human mammary adipocytes (M-Ads)-cancer crosstalk. As for other types of isolated white adipocytes, herein, we showed that human M-Ads die within 2-3 days by necrosis when grown in 2D. As an alternative, M-Ads were grown in a fibrin matrix, a 3D model that preserve their distribution, integrity and metabolic function for up to 5 days at physiological glucose concentrations (5 mM). Higher glucose concentrations frequently used in in vitro models promote lipogenesis during M-Ads culture, impairing their lipolytic function. Using transwell inserts, the matrix embedded adipocytes were cocultured with breast cancer cells. FFA transfer between M-Ads and cancer cells was observed, and this event was amplified by obesity. Together these data show that our 3D model is a new tool for studying the effect of M-Ads on tumor cells and beyond with all the components of the tumor microenvironment including the immune cells.

Evaluation of Pre-Therapeutic Assessment in Endometrial Cancer Staging.

OBJECTIVE: The aim of this retrospective cohort study is to evaluate the concordance between the preoperative MRI and histology data with the final histopathological examination. METHOD: This is a retrospective observational study of 183 patients operated for endometrioid cancer between January 2009 and December 2019 in the surgical oncology department of the Lorraine Cancer Institute (ICL) in Vandœuvre-lès-Nancy. The patients included are all women operated on for endometrioid-type endometrial cancer over this period. The exclusion criteria are patients for whom the pre-therapy check-up does not include pelvic MRI and those who have not had first-line surgery. The final anatomopathological results were compared with preoperative imaging data and with endometrial biopsy data. RESULTS: For the myometrial infiltration, the sensitivity of MRI was of 37% and the specificity of 54%. To detect nodal metastases, the sensitivity of MRI was of 21% and the specificity of 93%. We observed an under estimation of the FIGO classification (p = 0.001) with the MRI in 42.7% of cases (n = 76) and an overestimation in 24.2% of cases (n = 43). There was a concordance in 33.1% of cases (n = 59). We had a poor agreement between the MRI and final histopathological examination with an adjusted kappa (κ) of 0.12 [95% IC (0.02; 0.24)]. There was a moderate concordance on the grade between the pretherapeutic biopsy and the final histopathological examination on excised tissue with an adjusted kappa of 0.52 [95% IC 0.42-0.62)]. Endometrial biopsy underestimated the tumor grade in 28.9% of cases (n = 50) (p < 0.001), overestimated the tumor grade in 6.9% of cases (n = 12) and we observed a concordance in 64.2% of cases (n = 111). CONCLUSION: The pre-operative assessment of endometrial cancer is inconsistent with the results obtained on final histopathological examination. A study with a systematic review should be done to assess the performance of MRI, only in expert centers, in order to consider a a specific care management for endometrial cancer patients: patients who have had an MRI in an outpatient center should have their imaging systematically reviewed, with the possibility of a new examination in case of incomplete sequences, by expert radiologists, and discussed in multidisciplinary concertation meeting in expert centers, before any therapeutic decision. The sentinel node biopsy must be used for low and intermediate risk endometrial cancer.