Preclinical murine tumor models: A structural and functional perspective
- Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104, F-75014, France
- UCLouvain, Belgium
Figures
Figure 1
Fibronectin expression is restricted to stromal cells in PyMT tumors, but not in tumors that have undergone EMT.
In the MMTV-PyMT model, fibronectin is only expressed by stromal cells, if the tumor is (A) spontaneous (SP) or (B) results from an orthotopical implant (TP) of cells dissociated from a SP tumor. Fibronectin may also be expressed by all tumor cells after EMT has taken place in (C) the TC1 cell line, here transplanted subcutaneously, or in (D) a spontaneous melanoma, TiRP. Tumor pieces were fixed overnight with periodate-lysine-paraformaldehyde at 4°C. Then, tumor samples were embedded in 5% low-gelling temperature agarose prepared in phosphate-buffered saline (PBS). 350 μm slices were cut with a vibratome in a bath of ice-cold PBS. Immunostaining of surface markers was performed at 37°C for 15 min with antibodies specific to EpCAM-BV421, CD31-Biot (both BD Pharmingen) or Fibronectin (Abcam). CD31-Biot was revealed with a streptavidin-PE (BD Pharmingen) and fibronectin with a goat anti-rabbit-FITC (Invitrogen).
Figure 2
Growth rate of TP and SP PyMT tumors.
(A) The growth of TP tumors slows down with time. (B) The growth of SP tumors, which is initially slow, accelerates with time. Data from 45 tumors from 45 TP mice and 26 tumors from 9 SP mice. The small and large tumor diameters, d and D, were measured with calipers. Tumor volume was approximated by the volume of a spheroid (d2.D/2). For each tumor, the volume at time day x is expressed relative to its volume at day 0, when the tumor volume was ~ 50–150 mm3. The ratios (volume(dx)/volume(d0)) expressed on a Log2 scale, are represented as a function of time.
Figure 3
DMXAA induces a transient regression of TP melanomas but not of isogenic SP tumors.
(A) B10.D2 mice were injected subcutaneously with 2 million T429.11 cells, a cell line derived from an induced Amela TiRP tumor (Zhu et al., 2017) (TP tumors). (B) TiRP mice were treated subcutaneously with 2 mg of 4-OH tamoxifen to induce tumor development as described in Zhu et al. (2017) (SP tumors). Tumor growth was measured with calipers and approximated to the volume of a spheroid (d2.D/2). When the average diameter was between 7 and 9 mm, T429-tumor-bearing mice or TiRP-tumor-bearing mice were randomized into two groups, with an average tumor volume of 220 mm3, and were treated with a single intraperitoneal (i.p.) injection of DMXAA (23 mg/kg) or DMSO (day 0). Tumor growth was monitored. Graphs show means ± S.E.M.
Tables
Table 1
Structural and functional comparison of SP and TP tumors.
| SP vs TP | Subcutaneous (s.c.) TP vs orthotopic (ortho.)TP | References | ||
|---|---|---|---|---|
| Vasculature fragility | TP > SP | Ortho > s.c. | Fenton et al. (2001); Drees et al. (2015); Guerin et al. (2019); Fung et al. (2015) | |
| Vasculature growth rate | TP > SP | This review | ||
| Tumor architecture | SP > TP SP = TP | This review Weiss et al. (2017); Guerin et al. (2019) | ||
| Tumor growth rate | TP > SP TP = SP | Wexler et al. (1965); McCredie et al. (1971); Rous (1914); Burton and Begg (1961); Zhu et al. (2017) | ||
| TGFβ abundance | SP > TP | Ortho > s.c. | Guerin et al. (2019); Zhu et al. (2017); Choudhury et al. (2004) | |
| Spontaneous immune response | TP > SP | Anders et al. (2017) | ||
| Tumor-associated macrophage (TAM) renewal rate | TP > SP | Strachan et al. (2013); Franklin et al. (2014) | ||
| Myeloid-derived suppressor cell (MDSC) abundance | SP > TP | Ortho > s.c. | Coffelt and de Visser (2015); Zhu et al. (2017); Guerin et al. (2019); Devaud et al. (2014) | |
| Sensitivity to | Immunogenic cell death (ICD)-based chemotherapy | TP only | Ciampricotti et al. (2012); Coffelt and de Visser (2015) | |
| Stimulator of interferon genes protein (STING) agonists | TP only | Guerin et al. (2019) | ||
| Adoptive transfer of T cells | TP > SP | Zhu et al. (2017) | ||
| Vaccination | TP only | Old et al. (1961); Hirsch (1962); Reilly et al. (2000); Ercolini et al. (2003) | ||
| Cortisone | TP > SP | Burton and Begg (1961) | ||
| Interleukin-12 (IL-12) | TP only | Lee et al. (2002) | ||
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Preclinical murine tumor models: A structural and functional perspective
eLife 9:e50740.
https://doi.org/10.7554/eLife.50740
