Wounding promotes ovarian cancer progression and decreases efficacy of cisplatin in a syngeneic mouse model

Abstract

BackgroundPrimary cytoreductive surgery followed by adjuvant chemotherapy is the standard treatment for advanced epithelial ovarian cancer. The average interval between surgery and chemotherapy initiation is approximately 4-weeks at most centers; however, since surgery may accelerate residual tumor growth, a shorter interval may be more beneficial.MethodsThe murine ID8 cell model of ovarian cancer was used to examine the efficacy of cisplatin treatment administered perioperatively or 7 days after surgical wounding. Luciferase-expressing cells ID8 cells were injected intraperitoneally (i.p.) into female C57/Bl6 mice. Fourteen days post-injection, animals received an abdominal incision or anesthesia alone and received i.p. cisplatin either on the surgical day or 7 days later, or received no chemotherapy. Additional animals received cisplatin 28 days after wounding for comparison.ResultsAbdominal tumor mass increased 2.5-fold in wounded vs. unwounded animals as determined by bioluminescent in vivo tumor imaging. Cisplatin administered on the day of wounding decreased tumor burden by 50%, as compared to 90% in unwounded animals. Cisplatin on day 7 or day 28 decreased tumor burden by 80 and 37% respectively.ConclusionsSurgical wounding increases ovarian tumor mass and decreases perioperative cisplatin efficacy in this animal model. Administration of cisplatin 1 week after surgery was more effective than cisplatin administered perioperatively or 4 weeks after surgery.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0428-6) contains supplementary material, which is available to authorized users.

Surgical trauma‐induced immunosuppression in cancer: Recent advances and the potential therapies

“…In metastatic mouse breast cancer‐bearing mice, injection of wound fluid close to the tumor site containing cytokines or growth factors accelerated the tumor growth 95,96 . Wounding after surgery increased ovarian tumor mass and decreased perioperative cisplatin efficacy in a separate study 97 . Besides promoting the growth of cancer cells, most of the signaling molecules and cells involved in wound healing have also play a role in escape from tumor dormancy and the development of metastases 98 …”

Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases

“…Recent results show that chemotherapy-generated cell death can paradoxically promote tumor growth via the release of proinflammatory and proangiogenic cytokines (9,10,18). Moreover, a preoperative cycle of chemotherapy can stimulate proinflammatory cytokines after cancer surgery (19), and surgical wounding may impair the efficacy of chemotherapy (20).…”

Clinical factors associated with prognosis in low-grade serous ovarian carcinoma: experiences at two large academic institutions in Korea and Taiwan

“…There has been a long-standing issue that surgery-induced accelerated tumor growth may lead to poor prognosis and demised survivals on solid tumors from delayed adjuvant chemotherapy after surgery supports this. As the earlier initiation of adjuvant chemotherapy may alleviate this negative effect of surgery, TTC is considered a prognostic factor in HGSOC [40][41][42] . For LGSOC, no study was conducted to see the effect of TTC on survival amid its biologic difference (relatively slow growing tumor of LGSOC) and different platinum sensitivity (relatively insensitive to platinum) from those of HGSOC, which may affect the effect of TTC on prognoses.…”