![]() daily into the proximity of tumor-bearing sites starting 9 d after tumor cell inoculation. Wound fluid (40 μL) from 9-d-old wounds, serum, or plasma was injected s.c. ![]() into the suprascapular pocket 9 d after tumor cell inoculation. Remote wounding was performed as a 1-cm long, bilateral, dermal incision in the suprascapular region 9 d after tumor cell inoculation ( Fig. Care was taken not to injure the underlying mammary gland to avoid mechanical spread of tumor cells. Nine days later, under anesthesia (isoflurane to effect, buprenorphine 0.75μg/g body weight i.p.), the animals were wounded locally by performing a 1-cm long, full-thickness dermal incision above the previously inoculated mammary fat pads. 1 × 10 4 4T1 mouse metastatic breast cancer cells ( 11) were suspended in 50 μL of Dulbecco's PBS (DPBS Invitrogen) and injected through the skin using 28-G needles into the mammary fat pads IV/V and IX/X of female BALB/c mice (ages, 8 wk Charles River). We used a syngeneic, immunocompetent mouse model to study the effect of wounding on tumor progression ( Fig. These reports suggest a strong interaction between the wound and tumor microenvironments that can accelerate tumorigenesis and tumor progression.Īnimal model. It has also been shown that full thickness transcutaneous wounding is a sufficient event for tumor expression and growth in both Rous sarcoma virus–infected chickens and v-ras transgenic mice, demonstrating that acute wounding can promote tumorigenesis in a host that is already initiated by viral infection or by oncogene expression ( 8– 10). Likewise, the coinjection of wound fluid and melanoma cells resulted in increased tumor volumes ( 7). Tumor incidence and tumor volume are higher if melanoma or fibrosarcoma cells are injected into a wound compared with unwounded tissue ( 6, 7), indicating that a preexisting wound microenvironment facilitates the establishment of tumors from a tumor cell inoculate. Animal models have been used to define the influence of preexisting wounds on tumor cells or the influence of wounding on initiated hosts. Perhaps, the greatest risk is the presence of unsuspected microdeposits of tumor left behind after tumor resection. The effect of acute wounding, as occurs during biopsy or extirpative surgery on an existing tumor, has not been addressed. The mechanisms of wound-promoted tumorigenesis and tumor progression are not fully understood. Clinically, chronic wounds are associated with increased risk of tumor formation ( 4), as with squamous or basal cell carcinomas that originate from chronic skin wounds ( 5), implying that wound healing and tumorigenesis may not only share common physiologic features but may also influence each other. Hence, tumors have been described as “wounds that do not heal” ( 2) conversely “wounds may be regarded as a tumor which heals itself” ( 3). Wound healing and tumor progression both involve processes of cell proliferation, inflammation, and angiogenesis. Inflammatory cells orchestrate the migration and proliferation of a variety of cells leading to remodeling of the injured tissue and tissue repair ( 1). ![]() Initially, cytokines and other effector molecules are released from damaged tissue, initiating a rapid invasion of inflammatory cells into the wound that persists for several days. ![]() They leave behind injured tissue and initiate a wound healing response that is a sequence of tightly controlled events ( 1). ![]() Surgical procedures are frequently performed to confirm diagnosis and resect tumors. ĭuring their lifetime, ∼10% of American women will be afflicted by breast cancer. Here, we define an experimental model of wound-promoted tumor growth that will enable us to identify mechanisms and therapeutic targets to reduce the negative effect of tissue repair on residual tumors. The effect of wounding on tumor growth can be mimicked by acellular wound fluid, suggesting that T cells secrete or mediate secretion of cytokines or growth factors that then accelerate tumor growth. This effect is T cell–dependent, as local wounding had no effect on tumor growth in nu/nu mice. Our results show that wound stroma can unfavorably influence growth of nearby tumors. Injection of wound fluid close to the tumor site increased tumor growth, whereas in vitro wound fluid compared with serum increased the proliferation rate of 4T1 cells. Local, but not remote, wounding increased tumor size when compared with sham treatment. Metastatic mouse breast cancer cells (4T1) were orthotopically injected into the mammary fat pads of BALB/c mice, and animals were wounded locally by full thickness dermal incisions above the mammary fat pads or remotely above the scapula 9 days later. We investigated the influence of acute wounding on tumor growth in a syngeneic mouse breast cancer model. ![]()
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