Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models

Sabol, Rachel A.; Bowles, Annie C.; Côté, Alexandra; Wise, Rachel M.; O’Donnell, Benjamen T.; Matossian, Margarite D.; Hossain, Fokhrul; Burks, Hope E.; Valle, Luis Del; Miele, Lucio; Collins‐Burow, Bridgette M.; Burow, Matthew E.; Bunnell, Bruce A.

doi:10.1186/s13058-019-1153-9

Cited by 48 publications

(51 citation statements)

References 44 publications

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“…In a recent publication, patient-derived xenograft (PDX) model, tumours grown in the presence of obesity-altered adipose stem cells in SCID/beige mice had increased circulating HLA1 + human cells as well as increased numbers of CD44 + CD24 − cancer stem cells in the peripheral blood, the authors concluded leptin produced by obesity-altered adipose stem cells promotes metastasis. Others have found a negative association with BMI and CTC counts using the CellSearch device [31,32]. Further work is needed to assess this correlation between CTCs and BMI.…”

Section: Discussionmentioning

confidence: 95%

Circulating tumour cell enumeration does not correlate with Miller–Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

O’Toole

Spillane

Huang

et al. 2020

Breast Cancer Res Treat

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Purpose The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. Methods Twenty-six patients were recruited, and blood samples were taken pre-and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ 2 or ANOVA was performed in SPSS 24.0 statistics software for associations. Results 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. Conclusions Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre-and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.

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Section: Discussionmentioning

confidence: 95%

Circulating tumour cell enumeration does not correlate with Miller–Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

O’Toole

Spillane

Huang

et al. 2020

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…In a recent publication, patient-derived xenograft (PDX) model, tumours grown in the presence of obesity-altered adipose stem cells in SCID/beige mice had increased circulating HLA1 + human cells as well as increased numbers of CD44 + CD24cancer stem cells in the peripheral blood, the authors concluded leptin produced by obesity-altered adipose stem cells promotes metastasis. Others have found a negative association with BMI and CTC counts using the CellSearch device [31,32]. Further work is needed to assess this correlation between CTCs and BMI.…”

Section: Discussionmentioning

confidence: 95%

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

O'Toole

Spillane

Huang

et al. 2019

Preprint

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Background: Detection and enumeration of Circulating Tumour Cells (CTCs) has been evaluated in many cancers such as breast cancer. However, the full prognostic and predictive power of CTCs for cancer cannot currently be harnessed, and the association between pathological complete response in patients receiving neoadjuvant chemotherapy for breast cancer and CTCs is still not clear. The aim of this study was to assess if CTCs could be used to predict pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: 26 patients were recruited, and blood samples taken pre- and post-neoadjuvant chemotherapy. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets clusters/microemboli. Counts were then correlated to the pathological response as measured by the Miller-Payne grading system. The associations between CTCs and clusters and pathological variables were evaluated with χ2 or ANOVA tests performed in the SPSS 24.0 statistics software. Results: 89% of the patients had invasive ductal carcinoma and 11% invasive lobular carcinoma. At baseline 85% of patients had CTCs present and only 4 patients were CTC negative. Median baseline CTC count was 7 (0-161) CTCs per 3mls of whole blood. Post chemotherapy, 58% of the patients had an increase in CTCs. This change in CTC count did not correlate with the Miller Payne grade of response to chemotherapy. No significant association was identified between the number of CTCs and clinical characteristics, including patient age, receptor status, tumour grade, disease type, lymph node metastasis, lymphovascular space invasion, radiological response or clinical or pathological stage. However, we did observe a correlation between pre-treatment CTC counts and body mass index, p<0.05. Conclusions: There was no correlation between the pre- and post-chemotherapy total number of CTCs/clusters and the Miller Payne grade. It is not enough to evaluate pathological response for neoadjuvant chemotherapy for breast cancer patients utilising CTCs identified by Giemsa staining alone. Additional characterisation is needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in breast cancer patients undergoing neoadjuvant chemotherapy.

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“…The treatment of breast cancer MCF-7 cell line with leptin leads to a remarkable increase in the expression of EMT markers (including vimentin and Snail) along with a downregulation of the epithelial marker E-cadherin ( 62 ). Besides, leptin secreted by adipose stem cells is demonstrated to promote the mesenchymal phenotype in triple-negative breast cancer (TNBC) cells through increased expression of TWIST1, Serpine1, and SNAI2 ( 63 ). Mouse mammary tumor virus (MMTV)-Wnt-1 transgenic mice, which develop spontaneous breast cancer under a diet-induced obesity regimen, present increased leptin production, upregulated EMT gene expression, and reduced survival ( 64 ).…”

Section: Bmas and Mechanisms Associated With Cancer Cells Migration Amentioning

confidence: 99%

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Liu

Zhao

2020

Front. Oncol.

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Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

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Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models

Cited by 48 publications

References 44 publications

Circulating tumour cell enumeration does not correlate with Miller–Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Circulating tumour cell enumeration does not correlate with Miller–Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

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