Proliferation and adipocyte-breast cancer cell contact
Sanjib Chaudhary, Institute of Life Sciences
3 February 2016
I have read with great interest the article published by Ryu et al where they have reported a reduced proliferation in breast cancer cells which are in contact with the neighbouring adipocytes. Herein the authors have reviewed 528 surgical specimens of breast cancer patients and assessed the relative ratio of tumor-adipose contact with association with clinico-pathological features.
Firstly, figure. 1c indicated that the smaller and low-grade tumors show a higher degree of direct tumor-adipose contact which is in contradiction with the previously published report that showed to promote increased breast tumor progression and high tumor size [1-7], the phenomenon also observed in other cancers [8]. The adipocytes in contact with the tumor cells overexpress proteases such as matrix metalloproteinase-11, and proinflammatory cytokines (interleukin (IL)-6, IL-1β) as seen in breast tumor histological and in vitro co-culture studies, thus mediate invasiveness, migration and proliferation [7, 9, 10]. This phenomenon is also seen in other cancer cells [8]. Thus, it is still unclear if the smaller tumors and low grade tumors are a resultant of tumor-adipose contact?
Secondly, figure 1a, d and e show that breast tumor can be spatially defined into- adipose and gland side, and measured the mitotic index (both ER positive and negative tumors). However, it is demonstrated that co-injection of murine 3T3-F442A pre-adipocytes and MCF7 cells in SCID mice show progressive tumor growth and with large clusters of breast cancers in contact with adipocytes [11] as also observed in ER negative breast cancer cells [10]. Therefore, the association of mitotic index of tumor cells with ER status of the breast cancer patients (Fig. 1e) may be obscured?
1. Duong MN, Cleret A, Matera EL, Chettab K, Mathe D, Valsesia-Wittmann S, Clemenceau B, Dumontet C: Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity. Breast cancer research : BCR 2015, 17:57.
2. Renehan AG, Zwahlen M, Egger M: Adiposity and cancer risk: new mechanistic insights from epidemiology. Nature reviews Cancer 2015, 15:484-498.
3. Bertolini F, Petit JY, Kolonin MG: Stem cells from adipose tissue and breast cancer: hype, risks and hope. British journal of cancer 2015, 112:419-423.
4. van Kruijsdijk RC, van der Wall E, Visseren FL: Obesity and cancer: the role of dysfunctional adipose tissue. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2009, 18:2569-2578.
5. Muller C: Tumour-surrounding adipocytes are active players in breast cancer progression. Annales d'endocrinologie 2013, 74:108-110.
6. O'Rourke RW, Meyer KA, Neeley CK, Gaston GD, Sekhri P, Szumowski M, Zamarron B, Lumeng CN, Marks DL: Systemic NK cell ablation attenuates intra-abdominal adipose tissue macrophage infiltration in murine obesity. Obesity 2014, 22:2109-2114.
7. Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, et al: Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer research 2011, 71:2455-2465.
8. MC R: The role of Cancer-Associated Adipocytes (CAA) in the dynamic
interaction between the tumor and the host. Tumor-Associated Fibroblasts and their Matrix 2011, Springer. SBM ed:111-123.
9. Manabe Y, Toda S, Miyazaki K, Sugihara H: Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. The Journal of pathology 2003, 201:221-228.
10. Iyengar P, Combs TP, Shah SJ, Gouon-Evans V, Pollard JW, Albanese C, Flanagan L, Tenniswood MP, Guha C, Lisanti MP, et al: Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 2003, 22:6408-6423.
11. Liu E, Samad F, Mueller BM: Local adipocytes enable estrogen-dependent breast cancer growth: Role of leptin and aromatase. Adipocyte 2013, 2:165-169.
Proliferation and adipocyte-breast cancer cell contact
3 February 2016
I have read with great interest the article published by Ryu et al where they have reported a reduced proliferation in breast cancer cells which are in contact with the neighbouring adipocytes. Herein the authors have reviewed 528 surgical specimens of breast cancer patients and assessed the relative ratio of tumor-adipose contact with association with clinico-pathological features.
Firstly, figure. 1c indicated that the smaller and low-grade tumors show a higher degree of direct tumor-adipose contact which is in contradiction with the previously published report that showed to promote increased breast tumor progression and high tumor size [1-7], the phenomenon also observed in other cancers [8]. The adipocytes in contact with the tumor cells overexpress proteases such as matrix metalloproteinase-11, and proinflammatory cytokines (interleukin (IL)-6, IL-1β) as seen in breast tumor histological and in vitro co-culture studies, thus mediate invasiveness, migration and proliferation [7, 9, 10]. This phenomenon is also seen in other cancer cells [8]. Thus, it is still unclear if the smaller tumors and low grade tumors are a resultant of tumor-adipose contact?
Secondly, figure 1a, d and e show that breast tumor can be spatially defined into- adipose and gland side, and measured the mitotic index (both ER positive and negative tumors). However, it is demonstrated that co-injection of murine 3T3-F442A pre-adipocytes and MCF7 cells in SCID mice show progressive tumor growth and with large clusters of breast cancers in contact with adipocytes [11] as also observed in ER negative breast cancer cells [10]. Therefore, the association of mitotic index of tumor cells with ER status of the breast cancer patients (Fig. 1e) may be obscured?
1. Duong MN, Cleret A, Matera EL, Chettab K, Mathe D, Valsesia-Wittmann S, Clemenceau B, Dumontet C: Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity. Breast cancer research : BCR 2015, 17:57.
2. Renehan AG, Zwahlen M, Egger M: Adiposity and cancer risk: new mechanistic insights from epidemiology. Nature reviews Cancer 2015, 15:484-498.
3. Bertolini F, Petit JY, Kolonin MG: Stem cells from adipose tissue and breast cancer: hype, risks and hope. British journal of cancer 2015, 112:419-423.
4. van Kruijsdijk RC, van der Wall E, Visseren FL: Obesity and cancer: the role of dysfunctional adipose tissue. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2009, 18:2569-2578.
5. Muller C: Tumour-surrounding adipocytes are active players in breast cancer progression. Annales d'endocrinologie 2013, 74:108-110.
6. O'Rourke RW, Meyer KA, Neeley CK, Gaston GD, Sekhri P, Szumowski M, Zamarron B, Lumeng CN, Marks DL: Systemic NK cell ablation attenuates intra-abdominal adipose tissue macrophage infiltration in murine obesity. Obesity 2014, 22:2109-2114.
7. Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, et al: Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer research 2011, 71:2455-2465.
8. MC R: The role of Cancer-Associated Adipocytes (CAA) in the dynamic
interaction between the tumor and the host. Tumor-Associated Fibroblasts and their Matrix 2011, Springer. SBM ed:111-123.
9. Manabe Y, Toda S, Miyazaki K, Sugihara H: Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. The Journal of pathology 2003, 201:221-228.
10. Iyengar P, Combs TP, Shah SJ, Gouon-Evans V, Pollard JW, Albanese C, Flanagan L, Tenniswood MP, Guha C, Lisanti MP, et al: Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 2003, 22:6408-6423.
11. Liu E, Samad F, Mueller BM: Local adipocytes enable estrogen-dependent breast cancer growth: Role of leptin and aromatase. Adipocyte 2013, 2:165-169.
Competing interests
No conflict of interests exist