Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding

Barbara Belletti, Jayant S. Vaidya, Sara D'Andrea, Frank Entschladen, Mario Roncadin, Francesca Lovat, Stefania Berton, Tiziana Perin, Ezio Candiani, Sonia Reccanello, [No Value] AndreaVeronesi, Vincenzo Canzonieri, Mauro G. Trovò, Kurt S. Zaenker, Alfonso Colombatti, Gustavo Baldassarre, Samuele Massarut

Research output: Contribution to journalArticle

Abstract

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 normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted/ntraoperativeradioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activationof 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 comparedwith 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.

Original languageEnglish
Pages (from-to)1325-1332
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number5
DOIs
Publication statusPublished - Mar 1 2008

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Radiotherapy
Cell Proliferation
Breast Neoplasms
Signal Transduction
Recurrence
Neoplasms
Tumor Microenvironment
Segmental Mastectomy
Wounds and Injuries
Risk Reduction Behavior
Proteomics
Wound Healing
Cell Movement
Research Design
Cytokines
Cell Line
Growth
Surgical Wound
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. / Belletti, Barbara; Vaidya, Jayant S.; D'Andrea, Sara; Entschladen, Frank; Roncadin, Mario; Lovat, Francesca; Berton, Stefania; Perin, Tiziana; Candiani, Ezio; Reccanello, Sonia; AndreaVeronesi, [No Value]; Canzonieri, Vincenzo; Trovò, Mauro G.; Zaenker, Kurt S.; Colombatti, Alfonso; Baldassarre, Gustavo; Massarut, Samuele.

In: Clinical Cancer Research, Vol. 14, No. 5, 01.03.2008, p. 1325-1332.

Research output: Contribution to journalArticle

Belletti, B, Vaidya, JS, D'Andrea, S, Entschladen, F, Roncadin, M, Lovat, F, Berton, S, Perin, T, Candiani, E, Reccanello, S, AndreaVeronesi, NV, Canzonieri, V, Trovò, MG, Zaenker, KS, Colombatti, A, Baldassarre, G & Massarut, S 2008, 'Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding', Clinical Cancer Research, vol. 14, no. 5, pp. 1325-1332. https://doi.org/10.1158/1078-0432.CCR-07-4453
Belletti, Barbara ; Vaidya, Jayant S. ; D'Andrea, Sara ; Entschladen, Frank ; Roncadin, Mario ; Lovat, Francesca ; Berton, Stefania ; Perin, Tiziana ; Candiani, Ezio ; Reccanello, Sonia ; AndreaVeronesi, [No Value] ; Canzonieri, Vincenzo ; Trovò, Mauro G. ; Zaenker, Kurt S. ; Colombatti, Alfonso ; Baldassarre, Gustavo ; Massarut, Samuele. / Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 5. pp. 1325-1332.
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AU - Belletti, Barbara

AU - Vaidya, Jayant S.

AU - D'Andrea, Sara

AU - Entschladen, Frank

AU - Roncadin, Mario

AU - Lovat, Francesca

AU - Berton, Stefania

AU - Perin, Tiziana

AU - Candiani, Ezio

AU - Reccanello, Sonia

AU - AndreaVeronesi, [No Value]

AU - Canzonieri, Vincenzo

AU - Trovò, Mauro G.

AU - Zaenker, Kurt S.

AU - Colombatti, Alfonso

AU - Baldassarre, Gustavo

AU - Massarut, Samuele

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N2 - 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 normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted/ntraoperativeradioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activationof 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 comparedwith 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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