Possible predictive markers related to micro-metastasis in breast cancer patients

Zhu, Li; Loo, Wings T.Y.; Cheng, Carter W.N.; Chow, Louis W C

doi:10.3892/or.15.5.1217

Cited by 9 publications

(9 citation statements)

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“…Some studies have suggested that the prognosis of breast cancer and its level of malignancy are closely associated with clinical factors such as patient age, clinical stage, and lymph node metastasis [11]. In this study, however, the authors did not notice statistically significant correlation of TGF-b1 and BRCA2 protein expression in breast cancer tissue with clinical factors such as age, number of axillary lymph node metastasis and ER/PR expression.…”

Section: Discussionmentioning

confidence: 78%

TGF-β1 and BRCA2 Expression are Associated with Clinical Factors in Breast Cancer

Zhu

Chen

et al. 2011

Cell Biochem Biophys

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The objective of this study was to investigate the possible association between the expression of transforming growth factor beta-1 (TGF-β1) and breast cancer type2 susceptibility protein (BRCA2) with clinical factors in breast cancer. TGF-β1, BRCA2, human epidermal growth factor receptor2 (HER2), estrogen receptor, and progesterone receptor protein levels were measured in 67 samples from breast cancer patients by immunohistochemistry. The expression of these proteins was correlated with various clinical factors including age, pathohistological grade and status of axillary lymph node implication. TGF-β1 and BRCA2 were expressed in breast cancer tissues and expression of HER2 and TGF-β1 was significantly correlated with BRCA2. The authors conclude that elevated expression of BRCA2 correlates with TGF-β1 and HER2 in breast cancer and these three factors act in synergy to promote cancer. Thus, detection of both TGF-β1 and BRCA2 may therefore assist in the prognosis and treatment of breast cancer.

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Section: Discussionmentioning

confidence: 78%

TGF-β1 and BRCA2 Expression are Associated with Clinical Factors in Breast Cancer

Zhu

Chen

et al. 2011

Cell Biochem Biophys

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“…Breast cancer patients have higher levels of PDGF and VEGF in both tumors and sera compared to normal controls [ 49 ]. PDGF-B expression predicts micrometastases in peripheral blood, bone marrow and sentinel lymph nodes of breast cancer patients [ 50 ], and plays a key role in initiating the desmoplastic response [ 24 , 25 ]. A recent study suggests that the PDGF pathway also plays a key role in therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling

Pinto

Dye²,

Jacobsen

et al. 2014

BMC Cancer

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BackgroundLuminal, estrogen receptor-positive breast cancers represent more than 70% of cases. Despite initial good prognoses one third of Luminal cancers eventually recur locally or at distant sites and exhibit hormone resistance. Here we demonstrate that factors elaborated by malignant stromal cells can induce Luminal tumor cells proliferation and promote angiogenesis and hormone independence. We recently isolated a malignant mouse mammary gland stromal cell line named BJ3Z that increases proliferation and angiogenesis in estrogen-free xenografted Luminal MCF-7 breast cancer cells.MethodsBJ3Z and Normal mouse mammary Fibroblasts (NMFs) were expression profiled using microarray assays. Messenger RNA levels were confirmed by RT-PCR and by immunohistochemistry (IHC). Breast cancer MCF-7, BT-474, BT-20 and MDA-MB-231cell lines and stromal BJ3Z and NMFs were grown for in vitro assays: breast cancer cell lines were treated with stromal cells conditioned media, for three-dimensional (3D) mono and co-cultures in Matrigel, proliferation was measured by Bromo-deoxyuridine (BrdU) incorporation using IHC. Tubule formation in vitro, a proxy for angiogenesis, was assessed using 3D cultured Human Umbilical cord Vascular Endothelial Cells (HUVEC).ResultsWe show that under estrogen-free conditions, BJ3Z cells but not NMFs increase proliferation of co-cultured Luminal but not basal-like human breast cancer cells in 2D or as 3D Matrigel colonies. Gene expression profiling, RT-PCR analysis and IHC of colony-derived BJ3Z cells and NMFs shows that Platelet Derived Growth Factor ligands (PDGF-A and -B) are elaborated by BJ3Z cells but not NMFs; while PDGF receptors are present on NMFs but not BJ3Z cells. As a result, in colony co-culture assays, BJ3Z cells but not NMFs increase MCF-7 cell proliferation. This can be mimicked by direct addition of PDGF-BB, and blocked by the PDGF receptor inhibitor Imatinib Mesylate. Both normal and malignant stromal cells enhance angiogenesis in an in vitro model. This effect is also due to PDGF and is suppressed by Imatinib.ConclusionsWe provide evidence that Luminal breast cancer cells can be targeted by the PDGF signaling pathway leading to estrogen-independent proliferation and angiogenesis. We speculate that stroma-directed therapies, including anti-PDGFR agents like Imatinib, may be useful in combination with other therapies for treatment of luminal cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-735) contains supplementary material, which is available to authorized users.

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“…Genetic markers such as TP53, VEGF, MAM, PTGS2, NME1, and other cancer genes (Abdul-Rasool et al, 2006;Nissan et al, 2006;Zhu et al, 2006) have been shown to have significant prognostic potential in breast cancer with respect to the axillary and systemic metastasis. New information is now emerging from the data obtained from genome-wide studies using high-throughput methodologies where many genes show different characteristics in expression profiles, which can affect the clinical outcome including the development of lymph node metastases (Bertucci et al, 2000;Ahr et al, 2001;van 't Veer et al, 2002).…”

mentioning

confidence: 99%

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases

Santos

Cavalli

Ribeiro

et al. 2008

Cytogenet Genome Res

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The sentinel lymph node (SLN) is considered to be the first axillary node that contains malignant cells in metastatic breast tumors, and its positivity is currently used in clinical practice as an indication for axillary lymph node dissection. Therefore, accurate evaluation of the SLN for the presence of breast metastatic cells is essential. The main aim of our study is to characterize the genomic changes present in the SLN metastatic samples with the ultimate goal of improving the predictive value of SLN evaluation. Twenty paired samples of SLN metastases and their corresponding primary breast tumors (PBT) were investigated for DNA copy number changes using comparative genomic hybridization (CGH). Non-random DNA copy number changes were observed in all the lesions analyzed, with gains being more common than losses. In 75% of the cases there was at least one change common to both PBT and SLN. The most frequent changes detected in both lesions were gains of 1pter→p32, 16, 17, 19, and 20 and losses of 6q13→q23 and 13q13→q32. In the PBT group, alterations on chromosomes 1, 16, and 20 were the most frequent, whereas chromosomes 1, 6, and 19 were the ones with the highest number of changes in the SLN metastatic group. A positive correlation was found between the DNA copy number changes per chromosome in each of the groups. Our findings indicate the presence of significant DNA copy number changes in the SLN metastatic lesions that could be used in the future as additional markers to improve the predictive value of SLN biopsy procedure.

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Possible predictive markers related to micro-metastasis in breast cancer patients

Cited by 9 publications

References 52 publications

TGF-β1 and BRCA2 Expression are Associated with Clinical Factors in Breast Cancer

TGF-β1 and BRCA2 Expression are Associated with Clinical Factors in Breast Cancer

Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases

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