Dataset Information

Wounds Inhibit Tumor Growth In Vivo.

ABSTRACT:

Objective

The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo.

Summary of background data

Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo.

Methods

To determine the interaction of tumors and wounds, we developed a tumor xenograft/allograft (human head and neck squamous cell carcinoma SAS/mouse breast carcinoma 4T1) wound mouse model. We examined tumor growth with varying temporospatial placement of tumors and wounds or ischemic flap. In addition, we developed a tumor/wound parabiosis model to understand the ability of tumors and wounds to recruit circulating progenitor cells.

Results

Tumor growth inhibition by full thickness excisional wounds was dose-dependent, maintained by sequential wounding, and relative to distance. This effect was recapitulated by placement of an ischemic flap directly adjacent to a xenograft tumor. Using a parabiosis model, we demonstrated that a healing wound was able to recruit significantly more circulating progenitor cells than a growing tumor. Tumor inhibition by wound was unaffected by presence of an immune response in an immunocompetent model using a mammary carcinoma. Utilizing functional proteomics, we identified 100 proteins differentially expressed in tumors and wounds.

Conclusion

Full thickness excisional wounds have the ability to inhibit tumor growth in vivo. Further research may provide an exact mechanism for this remarkable finding and new advances in wound healing and tumor biology.

SUBMITTER: Hu MS

PROVIDER: S-EPMC7169436 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Wounds Inhibit Tumor Growth In Vivo.

Hu Michael S MS Maan Zeshaan N ZN Leavitt Tripp T Hong Wan Xing WX Rennert Robert C RC Marshall Clement D CD Borrelli Mimi R MR Zhu Ted N TN Esquivel Mikaela M Zimmermann Andrew A McArdle Adrian A Chung Michael T MT Foster Deshka S DS Jones Ruth Ellen RE Gurtner Geoffrey C GC Giaccia Amato J AJ Lorenz H Peter HP Weissman Irving L IL Longaker Michael T MT

Annals of surgery 20210101 1

<h4>Objective</h4>The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo.<h4>Summary of background data</h4>Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo.<h4>Methods</h4>To determine the interaction of tumors and wounds, we devel ...[more]

PMID: 30829705

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Project description:In the past ten years, many studies have shown that malignant tissue has been "normalized" in vitro using mechanical signals. We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a "constraint field" on tumor growth. The human breast cancer cell line, MDA MB 231, admixed with ferric nanoparticles was grafted subcutaneously in Nude mice. The magnetizable particles rapidly surrounded the growing tumor. Two permanent magnets located on either side of the tumor created a gradient of magnetic field. Magnetic energy is transformed into mechanical energy by the particles acting as "bioactuators", applying a constraint field and, by consequence, biomechanical stress to the tumor. This biomechanical treatment was applied 2 hours/day during 21 days, from Day 18 to Day 39 following tumor implantation. The study lasted 74 days. Palpable tumor was measured two times a week. There was a significant in vivo difference between the median volume of treated tumors and untreated controls in the mice measured up to D 74 (D 59 + population): (529 [346; 966] mm3 vs 1334 [256; 2106] mm3; p = 0.015), treated mice having smaller tumors. The difference was not statistically significant in the group of mice measured at least to D 59 (D 59 population). On ex vivo examination, the surface of the tumor mass, measured on histologic sections, was less in the treated group, G1, than in the control groups: G2 (nanoparticles, no magnetic field), G3 (magnetic field, no nanoparticles), G4 (no nanoparticles, no magnetic field) in the D 59 population (Median left surface was significantly lower in G1 (5.6 [3.0; 42.4] mm2, p = 0.005) than in G2 (20.8 [4.9; 34.3]), G3 (16.5 [13.2; 23.2]) and G4 (14.8 [1.8; 55.5]); Median right surface was significantly lower in G1 (4.7 [1.9; 29.2] mm2, p = 0.015) than in G2 (25.0 [5.2; 55.0]), G3 (18.0 [14.6; 35.2]) and G4 (12.5 [1.5; 51.8]). There was no statistically significant difference in the day 59+ population. This is the first demonstration of the effect of stress on tumor growth in vivo suggesting that biomechanical intervention may have a high translational potential as a therapy in locally advanced tumors like pancreatic cancer or primary hepatic carcinoma for which no effective therapy is currently available.

Dataset Information

Wounds Inhibit Tumor Growth In Vivo.

Objective

Summary of background data

Methods

Results

Conclusion

Publications

Wounds Inhibit Tumor Growth In Vivo.

Similar Datasets

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