scholarly journals Contribution of Heparan Sulphate Binding in CCL21-Mediated Migration of Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3462
Author(s):  
Irene del Molino del Barrio ◽  
Annette Meeson ◽  
Katie Cooke ◽  
Mohammed Imad Malki ◽  
Ben Barron-Millar ◽  
...  

Chemokine receptor CCR7 is implicated in the metastasis of breast cancer to the lymph nodes. Chemokine function is dependent upon their binding to both cell-surface heparan sulphate (HS) and to their specific receptors; thus, the role of HS in CCR7-mediated lymph node metastasis was investigated by creating a non-HS binding chemokine CCL21 (mut-CCL21). Mut-CCL21 (Δ103–134) induced leukocyte chemotaxis in diffusion gradients but did not stimulate trans-endothelial migration of PBMCs (p < 0.001) and 4T1-Luc cells (p < 0.01). Furthermore, the effect of heparin and HS on the chemotactic properties of wild-type (WT) and mut-CCL21 was examined. Interestingly, heparin and HS completely inhibit the chemotaxis mediated by WT-CCL21 at 250 and 500 µg/mL, whereas minimal effect was seen with mut-CCL21. This difference could potentially be attributed to reduced HS binding, as surface plasmon resonance spectroscopy showed that mut-CCL21 did not significantly bind HS compared to WT-CCL21. A murine model was used to assess the potential of mut-CCL21 to prevent lymph node metastasis in vivo. Mice were injected with 4T1-Luc cells in the mammary fat pad and treated daily for a week with 20 µg mut-CCL21. Mice were imaged weekly with IVIS and sacrificed on day 18. Luciferase expression was significantly reduced in lymph nodes from mice that had been treated with mut-CCL21 compared to the control (p = 0.0148), suggesting the potential to target chemokine binding to HS as a therapeutic option.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 757
Author(s):  
Sanaz Samiei ◽  
Renée W. Y. Granzier ◽  
Abdalla Ibrahim ◽  
Sergey Primakov ◽  
Marc B. I. Lobbes ◽  
...  

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51–68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41–0.74 and 0.48–0.89 in the training cohorts, respectively, and between 0.30–0.98 and 0.37–0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.


Author(s):  
Huswatun Hasanah ◽  
Rina Masadah ◽  
Berti J. Nelwan ◽  
Djumadi Achmad ◽  
Upik A. Miskad ◽  
...  

Background: Breast cancer is the second most common cancer in the world and is the most epidemic cancer in women, with approximately 1.67 million cases. Metastasis of tumor cells to other organs is a major cause of the increasing trend of mortality in breast cancer. This study aims to analyze the expression of c-Met associated with metastasis to axillary lymph nodes in invasive breast cancer.Method: The research was conducted at the Laboratory of Anatomical Pathology of Hasanuddin University Hospital. Stratified sampling was performed from January 2014 - January 2019. Immunohistochemical staining technique was applied upon 66 collected samples, followed by evaluating the c-Met expression score in invasive breast cancer group with positive and negative lymph node status.Result: c-Met overexpression was found among the invasive breast cancer incidence with lymph node metastasis. Among 50 cases with c-Met overexpression (c-Met positive), 40 cases (80%) of invasive breast cancer with lymph node metastasis were identified, while 10 cases (20%) were found in invasive breast cancer without metastasis to lymph nodes. On 16 cases with negative c-Met, 3 cases (18.8%) were found in invasive breast cancer with lymph node metastasis, and 13 cases (81.3%) in invasive breast cancer without metastasis to the lymph nodes. The statistical test results indicated a significant correlation between c-Met expression scores and metastasis to axillary lymph nodes in invasive breast cancer (p <0.001).Conclusion: As one of biomarkers, c-Met overexpression plays a vital role in the treatment of patients with invasive breast cancer to predict patient outcomes and to determine modalities. It is possible to apply c-Met overexpression to investigate aggressiveness of metastatic tumor cells in the future.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that cartilage oligomeric matrix protein, encoded by COMP, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that COMP was also differentially expressed in brain metastatic tissues5. COMP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of COMP in primary tumors was correlated with patient recurrence-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of COMP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that protein tyrosine phosphatase, receptor type C associated protein, encoded by PTPRCAP, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that PTPRCAP was also differentially expressed in brain metastatic tissues5. PTPRCAP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of PTPRCAP in primary tumors was correlated with patient distant metastasis-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of PTPRCAP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with lymph node metastasis in humans with metastatic breast cancer. We found that cluster of differentiation 226, encoded by CD226, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD226 was also differentially expressed in brain metastatic tissues (5). CD226 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of CD226 in primary tumors was correlated with patient overall survival in lymph node negative patients but not in lymph node positive patients. Modulation of CD226 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2018 ◽  
Vol 41 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Bahadır Öz ◽  
Alper Akcan ◽  
Serap Doğan ◽  
Ümmühan Abdulrezzak ◽  
Dicle Aslan ◽  
...  

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