Effect of 17β-estradiol on estrogen receptor negative breast cancer cells in an osteolytic mouse model

Osteolytic effects of tumoral estrogen signaling in an estrogen receptor-positive breast cancer bone metastasis model

“…Radiographs documenting proximal tibial and distal femoral osteolytic lesions, also common sites for ER− BMETs [ 59 ] , were also notable for clear evidence of E 2 -driven, albeit possibly differential, increases in bone density in mice of both ages [ Figure 1C ]. This observation raised questions about possible contributions of E 2 effects on the bone microenvironment ( vs. direct effects on ER+ tumors) in supporting ER+ MCF-7 BMET progression, a postulate further supported by findings in 5-week-old mice inoculated instead with osteotropic ER− MDA-MB-231 cells, where treatment with the same 0.72 mg E 2 dose led to an increase in osteolytic lesion size (3.5 ± 0.8-fold increased lesion size in E 2 -supplemented ( n = 12) vs. control mice ( n = 10), P < 0.01), but unchanged incidence (91.6% vs. 80.0%, P > 0.05), consistent with prior reports of pro-metastatic, anabolic E 2 bone effects in ER− BMET models [ 35 , 36 ] .…”

“…Larger osteolytic lesion sizes in young ( vs. mature) mice treated with the same E 2 dose appeared attributable to greater E 2 -mediated anabolism in young mice since tumor cell dissemination and proliferation were otherwise the same. Increased osteolytic BMET lesion size in E 2 -treated ( vs. control) mice inoculated with ER− breast cancer cells further confirmed a role of anabolic bone microenvironmental effects of E 2 in driving osteolytic breast cancer BMET progression, independent of tumoral ER signaling, consistent with previous similar reports in ER− BMET models [ 35 , 36 ] . Because these experiments provide the first evidence, to our knowledge, that bone anabolic effects of E 2 promote ER+ BMET progression subsequent to tumor cell dissemination to bone (as bone seeding was E 2 - and age-independent), this finding may have clinical implications when estrogens and/or other anabolic agents are used to treat osteoporosis in post-menopausal women [ 75 ] , an age where breast cancer incidence is the highest [ 76 ] and silent bone micrometastases may already be present prior to a ER+ breast cancer diagnosis [ 77 – 80 ] .…”

“…Evidence from ER-BMET models, which represent the majority of preclinical breast cancer BMET research, has allowed for an assessment of the influence of estrogenic effects on the bone microenvironment, independent of tumor cell ER signaling, on osteolytic ER− BMET progression. Taken together, these ER− breast cancer xenograft studies suggest that both induction of bone formation by E 2 -treatment [ 35 , 36 ] and bone resorption by E 2 -deprivation [via ovariectomy (OVX)] [ 28 , 37 , 38 ] promote ER− BMET progression. In ER+ BMET models, E 2 bone-microenvironmental effects have often not been considered [ 19 , 21 – 26 , 39 , 40 ] and are rarely documented [ 18 , 20 , 28 ] , while a role of tumor ERα signaling in driving tumor-associated osteolysis has not, to our knowledge, previously been studied.…”

MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis

“…A surgical bone implantation approach (described in Materials and Methods ) was used to examine the impact of RM1-BM- Luc tumor growth and to study the tumor-bone interface in mda-9 −/− animals ( 36 ). The absence of mda-9/syntenin profoundly affected tumor growth ( Fig.…”

In Vitro Investigations of miR-33a Expression in Estrogen Receptor-Targeting Therapies in Breast Cancer Cells

“…For example, combined treatment of 17-β-Estradiol with genistein showed a suppressive role on cell proliferation and survival in MDA-MB-231 cells through upregulating apoptotic markers [ 21 ]. However, individual treatment of 17-β-Estradiol enhanced the tumor progression and metastasis of triple-negative MDA-MB-231 breast cancer cells [ 23 ].…”