Role of HER2 in wound-induced breast carcinoma proliferation

Tagliabue, Elda; Agresti, Roberto; Carcangiu, Maria Luisa; Ghirelli, Cristina; Morelli, Daniele; Campiglio, Manuela; Martel, Maritza; Giovanazzi, Riccardo; Greco, Marco; Balsari, Andrea; Ménard, Sylvie

doi:10.1016/s0140-6736(03)14112-8

Cited by 146 publications

(125 citation statements)

References 26 publications

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“…All these clinical observations, coupled with the notion that surgery modifies the growth kinetics of breast cancer micrometastasis (8,9), support the hypothesis that surgery itself represents a perturbing factor for metastasis development in humans, as shown in animal models (10,11). Accordingly, axillary wound fluid (WF) derived from breast cancer patients induced proliferation of Her2/Neu -expressing breast carcinoma cells in vitro, an effect that could be abrogated by trastuzumab (12). Thus, it is possible that modification of the local microenvironment by surgery may alter the growth kinetics of cancer cells, supporting the ''seed and soil'' theory first proposed by Sir Stephen Paget to explain the pathogenesis of cancer metastasis (13,14).…”

mentioning

confidence: 58%

Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding

Belletti

Vaidya

Entschladen

et al. 2008

Clinical Cancer Research

202

192

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Purpose: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated.The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment. Experimental Design: We studied how normaland mammary carcinoma cell growth and motility are affectedby surgical wound fluids (WF), collectedover 24 hfollowingbreast-conserving surgery in 45 patients, 20 of whomhadreceivedadditionalTARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed. Results: WF stimulated proliferation, migration, and invasion of breast cancer cell lines.The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients. Conclusions: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT. It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents.

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confidence: 58%

Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding

Belletti

Vaidya

Entschladen

et al. 2008

Clinical Cancer Research

202

192

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“…Metastatic relapse after primary surgery of EBC can be thought as arising from clinically undetectable minimal residual disease after disruption of the complex interactions between cancer cells and tightly-regulated physiological tumor-control processes. These processes include stroma-generated growth factors, angiogenesis system and immune survey (Demicheli et al, 1997;Heimann and Hellman, 2000;Pupa et al, 2002), all being potentially affected by the surgical procedure itself (Fisher et al, 1989;Tagliabue et al, 2003). Consequently, protein peaks participating to our multiprotein index could theoretically stem from tumor cells and/or the host response, which both have the potential to modify qualitatively or quantitatively the serum proteome.…”

Section: Discussionmentioning

confidence: 99%

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

et al. 2005

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A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; Po0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

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“…It has been associated with poor clinical outcome such as shorter survival and short time to relapse (2,3). This has led to ErbB2 being a target for drug development.…”

mentioning

confidence: 99%

Herceptin Sensitizes ErbB2–Overexpressing Cells to Apoptosis by Reducing Antiapoptotic Mcl-1 Expression

Henson

Gibson

2006

Clinical Cancer Research

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Purpose: Monoclonal antibodies, such as herceptin and trastuzumab, against the epidermal growth factor receptor ErbB2 (also known as HER2/neu) are an effective therapy for breast cancer patients with overexpression of ErbB2. Herceptin, in combination with standard chemotherapy, such as taxol or etoposide, gives a synergistically apoptotic response in breast tumors. Experimental Design: The mechanism underlying this synergy between chemotherapy and herceptin treatment is not well understood. Herein, we have determined that addition of herceptin, sensitized breast cancer cell lines MDA-MB-231 and MCF-7 to etoposide-or taxol-induced apoptosis.Results: This treatment resulted in reduced expression of ErbB2 and the antiapoptotic Bcl-2 family member Mcl-1 in MDA-MB-231 cells. Using antisense oligonucleotides against Mcl-1, MDA-MB-231cells were rendered sensitive to etoposide-induced apoptosis similar to herceptin, but combined treatment of antisense against Mcl-1 and herceptin failed to give a significant increase in apoptosis. In 29 human breast tumors immunostained for ErbB2 and Mcl-1, we found that when ErbB2 was overexpressed, there was a corresponding increase in Mcl-1expression. Discussion: Using murine fibroblasts that express human ErbB2, but no other ErbB family member (NE2), these cells showed resistance to both taxol-and etoposide-induced apoptosis compared with parental cells. In addition, NE2 cells preferentially express the antiapoptotic Bcl-2 family member Mcl-1compared with parental cells, and treatment with herceptin reduces Mcl-1 expression. Taken together, these results suggest that herceptin sensitizes ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1protein levels.

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Role of HER2 in wound-induced breast carcinoma proliferation

Cited by 146 publications

References 26 publications

Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding

Targeted Intraoperative Radiotherapy Impairs the Stimulation of Breast Cancer Cell Proliferation and Invasion Caused by Surgical Wounding

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

Herceptin Sensitizes ErbB2–Overexpressing Cells to Apoptosis by Reducing Antiapoptotic Mcl-1 Expression

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