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Novel mouse mammary cell lines for in vivo bioluminescence imaging (BLI) of bone metastasis.

Bolin C, Sutherland C, Tawara K, Moselhy J, Jorcyk CL - Biol Proced Online (2012)

Bottom Line: The 4 T1.2 luc3 cell line was found to closely model the sites of metastases seen in human patients including lung, liver, and bone.High osteolytic activity of the 4 T1.2 luc3 cells in vivo in the bone microenvironment was also detected.The engineered 4 T1.2 luc3 and 66c14 luc2 cell lines described in this study are valuable tools for studying the cellular events moderating the metastasis of breast tumor cells to bone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, Boise State University, Boise, ID, USA. cjorcyk@boisestate.edu.

ABSTRACT

Background: Tumor cell lines that can be tracked in vivo during tumorigenesis and metastasis provide vital tools for studying the specific cellular mechanisms that mediate these processes as well as investigating therapeutic targets to inhibit them. The goal of this study was to engineer imageable mouse mammary tumor cell lines with discrete propensities to metastasize to bone in vivo. Two novel luciferase expressing cell lines were developed and characterized for use in the study of breast cancer metastasis to bone in a syngeneic mouse model.

Results: The 4 T1.2 luc3 and 66c14 luc2 cell lines were shown to have high levels of bioluminescence intensity in vitro and in vivo after orthotopic injection into mouse mammary fat pads. The 4 T1.2 luc3 cell line was found to closely model the sites of metastases seen in human patients including lung, liver, and bone. Specifically, 4 T1.2 luc3 cells demonstrated a high incidence of metastasis to spine, with an ex-vivo BLI intensity three orders of magnitude above the commercially available 4 T1 luc2 cells. 66c14 luc2 cells also demonstrated metastasis to spine, which was lower than that of 4 T1.2 luc3 cells but higher than 4 T1 luc2 cells, in addition to previously unreported metastases in the liver. High osteolytic activity of the 4 T1.2 luc3 cells in vivo in the bone microenvironment was also detected.

Conclusions: The engineered 4 T1.2 luc3 and 66c14 luc2 cell lines described in this study are valuable tools for studying the cellular events moderating the metastasis of breast tumor cells to bone.

No MeSH data available.


Related in: MedlinePlus

BLI of 66c14 luc and 4T1.2 luc cells in vivo . Tumor bioluminescence intensities from each of the (A) 66c14 luc and (B) 4 T1.2 luc tumor-bearing mice on day 25 after tumor cell injection are shown. 66c14 luc2 and 4 T1.2 luc3 exhibited the highest BLI intensity in vivo (green bars). Sequential images of (C) 66c14 luc2 and (D) 4 T1.2 luc3 tumor-bearing mice imaged ventrally by BLI once a week for 4 weeks are shown. 66c14 luc2 tumors continued to grow while 4 T1.2 luc3 tumors became necrotic between day 25 and 32. Data expressed as photon/sec (mean ± std dev; n=3).
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Figure 4: BLI of 66c14 luc and 4T1.2 luc cells in vivo . Tumor bioluminescence intensities from each of the (A) 66c14 luc and (B) 4 T1.2 luc tumor-bearing mice on day 25 after tumor cell injection are shown. 66c14 luc2 and 4 T1.2 luc3 exhibited the highest BLI intensity in vivo (green bars). Sequential images of (C) 66c14 luc2 and (D) 4 T1.2 luc3 tumor-bearing mice imaged ventrally by BLI once a week for 4 weeks are shown. 66c14 luc2 tumors continued to grow while 4 T1.2 luc3 tumors became necrotic between day 25 and 32. Data expressed as photon/sec (mean ± std dev; n=3).

Mentions: Next, BLI intensity of 66c14 luc and 4 T1.2 luc cells during tumor growth was assessed in vivo. Tumors from injected 66c14 luc2 cells produced the highest level of BLI intensity of all the 66c14 luc cells, averaging 8.29 × 109 photons/second on day 25 after tumor cell injection (Figure 4A; green, Figure 3). Tumors from injected 4 T1.2 luc3 cells produced the highest level of BLI intensity of all the 4 T1.2 luc cells, averaging 4.84 × 106 photons/second on day 25 after tumor cell injection (Figure 4B; green, Figure 3). Sequential images on days 18, 25, 32, and 39 of mice injected with the 66c14 luc2 cell line showed increasing BLI intensity at the tumor site correlating with increasing tumor size (Figure 4C). The BLI intensity of tumors from mice injected with 4 T1.2 luc3 cells started to decrease after day 25, likely due to the tumor-associated necrosis (Figure 4D).


Novel mouse mammary cell lines for in vivo bioluminescence imaging (BLI) of bone metastasis.

Bolin C, Sutherland C, Tawara K, Moselhy J, Jorcyk CL - Biol Proced Online (2012)

BLI of 66c14 luc and 4T1.2 luc cells in vivo . Tumor bioluminescence intensities from each of the (A) 66c14 luc and (B) 4 T1.2 luc tumor-bearing mice on day 25 after tumor cell injection are shown. 66c14 luc2 and 4 T1.2 luc3 exhibited the highest BLI intensity in vivo (green bars). Sequential images of (C) 66c14 luc2 and (D) 4 T1.2 luc3 tumor-bearing mice imaged ventrally by BLI once a week for 4 weeks are shown. 66c14 luc2 tumors continued to grow while 4 T1.2 luc3 tumors became necrotic between day 25 and 32. Data expressed as photon/sec (mean ± std dev; n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3473320&req=5

Figure 4: BLI of 66c14 luc and 4T1.2 luc cells in vivo . Tumor bioluminescence intensities from each of the (A) 66c14 luc and (B) 4 T1.2 luc tumor-bearing mice on day 25 after tumor cell injection are shown. 66c14 luc2 and 4 T1.2 luc3 exhibited the highest BLI intensity in vivo (green bars). Sequential images of (C) 66c14 luc2 and (D) 4 T1.2 luc3 tumor-bearing mice imaged ventrally by BLI once a week for 4 weeks are shown. 66c14 luc2 tumors continued to grow while 4 T1.2 luc3 tumors became necrotic between day 25 and 32. Data expressed as photon/sec (mean ± std dev; n=3).
Mentions: Next, BLI intensity of 66c14 luc and 4 T1.2 luc cells during tumor growth was assessed in vivo. Tumors from injected 66c14 luc2 cells produced the highest level of BLI intensity of all the 66c14 luc cells, averaging 8.29 × 109 photons/second on day 25 after tumor cell injection (Figure 4A; green, Figure 3). Tumors from injected 4 T1.2 luc3 cells produced the highest level of BLI intensity of all the 4 T1.2 luc cells, averaging 4.84 × 106 photons/second on day 25 after tumor cell injection (Figure 4B; green, Figure 3). Sequential images on days 18, 25, 32, and 39 of mice injected with the 66c14 luc2 cell line showed increasing BLI intensity at the tumor site correlating with increasing tumor size (Figure 4C). The BLI intensity of tumors from mice injected with 4 T1.2 luc3 cells started to decrease after day 25, likely due to the tumor-associated necrosis (Figure 4D).

Bottom Line: The 4 T1.2 luc3 cell line was found to closely model the sites of metastases seen in human patients including lung, liver, and bone.High osteolytic activity of the 4 T1.2 luc3 cells in vivo in the bone microenvironment was also detected.The engineered 4 T1.2 luc3 and 66c14 luc2 cell lines described in this study are valuable tools for studying the cellular events moderating the metastasis of breast tumor cells to bone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, Boise State University, Boise, ID, USA. cjorcyk@boisestate.edu.

ABSTRACT

Background: Tumor cell lines that can be tracked in vivo during tumorigenesis and metastasis provide vital tools for studying the specific cellular mechanisms that mediate these processes as well as investigating therapeutic targets to inhibit them. The goal of this study was to engineer imageable mouse mammary tumor cell lines with discrete propensities to metastasize to bone in vivo. Two novel luciferase expressing cell lines were developed and characterized for use in the study of breast cancer metastasis to bone in a syngeneic mouse model.

Results: The 4 T1.2 luc3 and 66c14 luc2 cell lines were shown to have high levels of bioluminescence intensity in vitro and in vivo after orthotopic injection into mouse mammary fat pads. The 4 T1.2 luc3 cell line was found to closely model the sites of metastases seen in human patients including lung, liver, and bone. Specifically, 4 T1.2 luc3 cells demonstrated a high incidence of metastasis to spine, with an ex-vivo BLI intensity three orders of magnitude above the commercially available 4 T1 luc2 cells. 66c14 luc2 cells also demonstrated metastasis to spine, which was lower than that of 4 T1.2 luc3 cells but higher than 4 T1 luc2 cells, in addition to previously unreported metastases in the liver. High osteolytic activity of the 4 T1.2 luc3 cells in vivo in the bone microenvironment was also detected.

Conclusions: The engineered 4 T1.2 luc3 and 66c14 luc2 cell lines described in this study are valuable tools for studying the cellular events moderating the metastasis of breast tumor cells to bone.

No MeSH data available.


Related in: MedlinePlus