Reduced proliferation in breast cancer cells contacting the neighboring adipocytes in human breast cancer tissues
© Ryu et al. 2015
Published: 2 July 2015
The process of tumor formation and progression is a result of the complex interaction between malignant epithelial cells and the various cell populations in the tumor microenvironment [1, 2]. Recently, the role of cancer-associated adipocytes in cancer progression has been an active area of research, and many studies have suggested a proinvasive and prometastatic effect of the cancer-associated adipocytes [3, 4]. The cancer-promoting effect of adipocytes seems to originate from their ability to induce inflammatory milieu and to provide an energy source for cancer cells [5, 6].
To overcome the issue of intertumoral heterogeneity, we semiquantitatively analyzed the histologic grade of cancer cells on the adipose side and on the gland side within the same tumor in 107 patients whose tumors had moderate tumor–adipose contact (between 0.4 and 0.6; Fig. 1d). We measured the degree of the tubule formation, nuclear pleomorphism, and mitotic count, which are the three components of the widely used Elston–Ellis modification of the Scarff–Bloom–Richardson histologic grading system for both adipose-side and gland-side tumor cells . The tumor cells on the adipose side showed significantly lower mitotic index when compared with that of the tumor cells on the gland side. The significant association with mitotic index and the cancer cells’ distance to the adipose tissue was only seen in estrogen receptor-negative breast tumors (Fig. 1e, representative case shown in Fig. 1f). There was no significant difference between the adipose-side and gland-side cells in tubule formation and nuclear pleomorphism.
In conclusion, our analysis of human breast cancer samples showed that tumor cells residing close to the adipose tissue showed significantly lower mitotic count than cells distant from the adipose tissue. Our findings suggest that, contrary to the prevailing concept of the cancer-promoting role of cancer-associated adipocytes, the true interaction between cancer cells and the neighboring adipose tissue can be a complex one.
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012R1A1A2005929), and by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (A1220200).
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