Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

Abstract

Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures.

The Composition of Surgical Wound Fluids from Breast Cancer Patients is Affected by Intraoperative Radiotherapy Treatment and Depends on the Molecular Subtype of Breast Cancer

“…It has been suggested, that invasive procedures (such as surgery or biopsy) affect the remaining tumor cells by improving their survival and by stimulating proliferation and migration [3,4]. One of the concepts explaining this phenomenon is the induction of wound healing responses, which are responsible for tissue repair in normal tissues.…”

“…However, the clinical and experimental data suggest that surgery itself may be responsible for local relapse and metastasis [2]. It has been demonstrated that invasive procedures (both surgery and biopsy) affect the remaining tumor cells, increasing their survival, proliferation, and migration [3,4]. One of the concepts explaining this phenomenon is the induction of a wound healing response.…”

“…However, induction of adaptive and innate immune response in tumor tissue stimulates cell survival, angiogenesis, and extravasation of circulating tumor cells. It has become evident that some types of immune response, or immune cells, can promote tumor progression more than others [3]. For example, tumor-resident macrophages (M2 polarized macrophages) secret vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), which induce angiogenesis and the recruitment of neutrophils contribute to tumor progression and metastasis [5,6].…”

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

“…The surgical trauma may enhance EMT and improve the migratory capacity of tumor cells mediated through soluble factors produced by inflammatory cells . In an in vitro model, the wound fluids from patients with breast cancer stimulated EMT.…”

“…Interestingly, in a lung cancer model, oncostatin knock‐out mice had reduced CTC, fewer lung metastases and increased overall survival . Furthermore, proteoglycans have been shown to be extensively involved in the migration of tumor cells as demonstrated by Chondroitin Sulfate A that mediates focal adhesion and motility, while blocking Chondroitin Sulfate A inhibited cellular migration and metastasis formation …”