Interleukin 6 signal transducer, IL6ST correlates with survival outcomes in invasive ductal carcinoma

2021 ◽  
Author(s):  
Glen Foley ◽  
George Brock ◽  
Taylan Burke
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Interleukin 6 ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
The United States ◽  
Breast Cancer Metastasis ◽  
Survival Outcomes ◽  
Signal Transducer ◽  
Transcriptome Data

In the United States, breast cancer is the most common cause of mortality among women (1). Breast cancer metastasis, or the spread of cancer from the breast to other organs such as the bones, liver, brain, and lungs, is the leading cause of death in women (2). We combined two separate microarray datasets, one containing transcriptome data from primary breast tumors (3) and the other containing transcriptome data from metastases in women with breast cancer (4), both of which included survival data for the patient from whom each tumor or metastasis sample was obtained. We discovered that the gene encoding the Interleukin 6 signal transducer, IL6ST, gp130 (5), was among the genes whose expression was most variable between patients who lived longer or less than 18 months by comparing tumor transcriptome data depending on survival outcomes. IL6ST was expressed at considerably higher levels in both original breast cancers and metastases in women who survived more than 18 months. These findings support the use of IL6ST as a biomarker or prognostic indicator (6-8) to help determine which women will benefit from more or less intensive treatment regimens based on metastasis prediction; additionally, IL6ST may be fundamentally linked to tumor progression and tumor aggressiveness, implying that IL6ST could be used as a therapeutic target in breast cancer.

scholarly journals Gene expression of the Interleukin 6 signal transducer, IL6ST (gp130) associates with survival outcomes in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Interleukin 6 ◽  
Prognostic Indicator ◽  
The United States ◽  
Survival Outcomes ◽  
Signal Transducer ◽  
Transcriptome Data ◽  
Primary Tumors ◽  
Treatment Regimens

Breast cancer is a leading cause of death for women in the United States (1). The central reason women die from breast cancer is metastasis, or spread of cancer from the breast to foreign sites such as the bones, liver, brain and lungs (2). We integrated independent microarray datasets, one containing transcriptome data from primary tumors of the breast (3), and the other containing transcriptome data from metastases from women with breast cancer (4), each of which possess survival data associated with the patient from which each tumor or metastasis sample was obtained. By comparing tumor transcriptome data based on survival outcomes, we found that gene encoding the Interleukin 6 signal transducer, IL6ST, gp130 (5), was among the genes whose expression was most different between patients who survived greater or less than 18 months. In both primary tumors of the breast and in metastases, IL6ST was expressed at significantly higher levels in women who survived greater than 18 months. These data are consistent with a role for IL6ST as a biomarker, or prognostic indicator (6-8) to help predict which women can benefit from more or less intensive treatment regimens based on prediction of metastasis; moreover, IL6ST may be fundamentally linked with tumor progression and tumor aggressiveness highlighting potential for IL6ST as a therapeutic target in breast cancer.

Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

2014 ◽  
Vol 29 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Masahiro Nakano ◽  
Tetsuro Masuda ◽  
Haruki Odagiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

scholarly journals A Case of 10-Year Survival after Adrenalectomy for Isolated Adrenal Metastasis of Breast Cancer

Reports ◽  
2020 ◽  
Vol 3 (3) ◽  
pp. 22
Author(s):  
Tsuyoshi Nakagawa ◽  
Goshi Oda ◽  
Akihiro Yano ◽  
Hiroshi Kawachi ◽  
Hiroyuki Uetake
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Radical Mastectomy ◽  
Breast Cancer Metastasis ◽  
Adrenal Metastasis ◽  
Pathological Examination ◽  
Endoscopic Adrenalectomy ◽  
Axillary Lymphadenectomy

Isolated adrenal metastasis of breast cancer is very rare, so adrenalectomy for breast cancer metastasis is rarely performed. The case of a breast cancer patient with five-year survival after resection of a left isolated adrenal metastasis is presented. A 70-year-old woman underwent left modified radical mastectomy and axillary lymphadenectomy for invasive ductal carcinoma (T2N1M0) 9 years earlier. At regular follow-up, a left adrenal mass, 4 cm in diameter, was seen on ultrasound examination and computed tomography (CT). Endoscopic adrenalectomy was performed. Pathological examination confirmed isolated adrenal metastasis of breast cancer. After surgery, hormone therapy was given for 5 years. Ten years after adrenalectomy, no metastatic lesions in other organs have been found on CT. Adrenalectomy for a metastatic adrenal tumor of breast cancer may provide survival benefits when combined with systemic hormone therapy and chemotherapy, particularly in patients with disease confined to the adrenal glands.

scholarly journals Aicardi-Goutières Syndrome gene Rnaseh2c is a metastasis susceptibility gene in breast cancer

2019 ◽  
Author(s):  
Sarah K. Deasy ◽  
Ryo Uehara ◽  
Suman K. Vodnala ◽  
Howard H. Yang ◽  
Randall A. Dass ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
The United States ◽  
Breast Cancer Metastasis ◽  
Rnase H2

AbstractBreast cancer is the second leading cause of cancer-related deaths in the United States, with the majority of these deaths due to metastatic lesions rather than the primary tumor. Thus, a better understanding of the etiology of metastatic disease is crucial for improving survival. Using a haplotype mapping strategy in mouse and shRNA-mediated gene knockdown, we identified Rnaseh2c, a scaffolding protein of the heterotrimeric RNase H2 endoribonuclease complex, as a novel metastasis susceptibility factor. We found that the role of Rnaseh2c in metastatic disease is independent of RNase H2 enzymatic activity, and immunophenotyping and RNA-sequencing analysis revealed engagement of the T cell-mediated adaptive immune response. Furthermore, the cGAS-Sting pathway was not activated in the metastatic cancer cells used in this study, suggesting that the mechanism of immune response in breast cancer is different from the mechanism proposed for Aicardi-Goutières Syndrome, a rare interferonopathy caused by RNase H2 mutation. These results suggest an important novel, non-enzymatic role for RNASEH2C during breast cancer progression and add Rnaseh2c to a panel of genes we have identified that together could determine patients with high risk for metastasis. These results also highlight a potential new target for combination with immunotherapies and may contribute to a better understanding of the etiology of Aicardi-Goutières Syndrome autoimmunity.Author SummaryThe majority of breast cancer-associated deaths are due to metastatic disease, the process where cancerous cells leave the primary tumor in the breast and spread to a new location in the body. To better understand the etiology of this process, we investigate the effects of gene expression changes in the primary tumor. In this study, we found that changing the expression of the gene Rnaseh2c changed the number of metastases that developed in the lungs of tumor-bearing mice. By investigating the enzyme complex Rnaseh2c is part of, RNase H2, we determined that Rnaseh2c’s effects may be independent of RNase H2 enzyme activity. Because Rnaseh2c is known to cause the autoimmune disease Aicardi-Goutières Syndrome (AGS), we tested whether the immune system is involved in the metastatic effect. Indeed, we found that the cytotoxic T cell response is important for mediating the effect that Rnaseh2c has on metastasis. Together these data indicate that Rnaseh2c expression contributes to a patient’s susceptibility to developing breast cancer metastasis and demonstrate that the immune system is involved in this outcome. The implications of this study suggest immunotherapy could be a viable treatment for breast cancer metastasis and may help inform the understanding of AGS and RNase H2 in cancer.

Fibroblasts Isolated from Common Sites of Breast Cancer Metastasis Enhance Cancer Cell Growth Rates and Invasiveness in an Interleukin-6–Dependent Manner

2008 ◽  
Vol 68 (21) ◽  
pp. 9087-9095 ◽  
Author(s):  
Adam W. Studebaker ◽  
Gianluca Storci ◽  
Jillian L. Werbeck ◽  
Pasquale Sansone ◽  
A. Kate Sasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Growth Rates ◽  
Interleukin 6 ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Dependent Manner ◽  
Cancer Cell Growth

scholarly journals The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Madhavi Puchalapalli ◽  
Liang Mu ◽  
Chevaunne Edwards ◽  
Benjamin Kaplan-Singer ◽  
Pearl Eni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
The United States ◽  
Breast Cancer Metastasis ◽  
Tumor Cell Adhesion ◽  
Tumor Environment

Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis.

scholarly journals BREAST CANCER METASTASIS TO THE THYROID GLAND: A RARE CASE REPORT WITH DIAGNOSTIC DILEMM

2020 ◽  
pp. 1-2
Author(s):  
Rajneesh Rawat ◽  
Sunil M Lanjewar ◽  
Mrinalini M Borkar ◽  
Jyoti Baghel
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Thyroid Gland ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Metastatic Lesion ◽  
Breast Cancer Metastasis ◽  
Breast Lump ◽  
Rare Case Report ◽  
Simple Mastectomy

Introduction: Metastasis to thyroid gland is very rare; with breast cancer metastasizing to thyroid is extremely rare. Here, we report a case of metastatic lesion in the thyroid from breast carcinoma in a 43 year old female who presented to us with a right breast lump for 1.5 years along with thyroid swelling for 6 months. Results: FNAC of breast lump showed ductal carcinoma while FNAC of thyroid nodule was inconclusive. CECT showed right breast neoplasm with malignant deposits in isthmus of thyroid. She underwent right simple mastectomy with axillary clearance and total thyroidectomy followed by chemotherapy. Histopathology analysis showed invasive ductal carcinoma in isthmus of thyroid.This was confirmed by immunohistochemistry, which revealed positive for GATA- 3and negative for TTF1 and Calcitonin. Conclusion: This case report highlights the importance of a correct early diagnostic work up.Immunohistochemical panels are helpful in differentiating between primary and secondary tumors.Also, thyroidectomy may be beneficial for local disease control and prevent the potential morbidity of tumor extension related to airway.

scholarly journals Rare Metastases in Colorectum of Infiltrating Ductal Breast Cancer: A Rare Case Report and Review

2020 ◽  
Author(s):  
Zhijun Zhang ◽  
Tao Li ◽  
Yuemin Li ◽  
Dongxu Li ◽  
Kai Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Ductal Carcinoma ◽  
Therapeutic Option ◽  
Radical Mastectomy ◽  
Left Breast ◽  
Breast Cancer Metastasis ◽  
Positron Emission ◽  
Rare Case Report ◽  
Lost To Follow Up

Abstract Background: Breast ductal carcinoma hardly metastasizes to colorectum and the effect of surgery is controversial. We treated one case of patients with breast ductal carcinoma metastasizes to colorectum with surgery and discussed current management experience of breast cancer metastasizing to colorectum by reviewing the literature. Case Presentation: A 37-year-old woman underwent a modified radical mastectomy three years ago for right breast cancer and developed left breast cancer with right breast cancer suspiciously metastasizing to colorectum, left ovary along with oviduct, pancreas, and left acetabulum according to positron emission tomography-computed tomography. Then she had chosen to give up further therapy but was admitted to our department complaining of shapeless feces and mucus pus and blood in stool for 2 years with the process of aggravating symptoms for recent 2 months. Colonoscopy revealed the existence of colorectal carcinoma. She received laparoscopic combined abdominal perineal resection and bilateral ovarian salpingectomy. Postoperative pathology as well as immunohistochemistry supported the origin of primary breast infiltrating ductal cancer. She remained tamoxifen therapy and was alive until she was lost to follow-up.Conclusions: Clinicians must pay attention to any gastro-intestinal symptoms of patients with a medical history of breast cancer since the incipient symptoms of breast cancer metastasis to colorectum are insidious. Definite diagnosis may be difficult even by endoscopy. Surgery should be considered as a therapeutic option and definite diagnostic means combined with immunohistochemistry.

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