I'm trying to study the effect of anti cancer drugs and would appreciate any input on the various osteosarcoma cell lines.
Dear Gabriela,
The following text fully covers the answer to your question:
2. In Vitro
2.1. Animal-Derived Cell Lines
The first successfully established metastatic osteosarcoma cell lines were derived from spontaneous mouse osteosarcoma (Figure 2) including cell lines K12 and K7M2 (developed from lung metastases of K7 cells in BALB/c mice) [13, 19, 25]. These lines were successfully proved to be metastatic and in later years used to assay the metastatic process of osteosarcoma [26]. Another murine osteosarcoma cell line, the Dunn cell line, and its derivative cell lines like LM8 were extensively used for screening new osteosarcoma drugs and studying the inhibitory effects of these compounds on angiogenesis and metastasis [27–36].
In contrast to K12 and K7M2 cells, UMR 106-01 was not a result of spontaneous osteosarcoma as it is originating from a 32P-induced tumor in a rat [37]. However, because of its in vitro and in vivo (in mouse tibia) exceptionally phenotypical similarities to human osteosarcoma, and the rapid formation of pulmonary metastasis, this cell line has been studied at length not only in osteosarcoma research [38] but also in several other bone-related studies [38–41].
A number of cell lines have been derived from spontaneous canine osteosarcoma (Figure 2). In particular, D-17 cell line originating from an osteosarcoma metastatic to the lung in an 11-year-old female poodle [42] was next to extensive use in viral studies, helpful for analyzing immunotherapy of hepatic micrometastases [43] as well as finding therapeutics for the treatment of bone cancer in dogs.
2.2. Human-Derived Cell Lines
Starting with the establishment of the first human osteosarcoma cell line named U2OS in 1964, many human osteosarcoma cell lines, such as HOS and SAOS2, have been successfully established (Figure 3). Despite comprehensive studies characterizing the U2OS cell line in vitro [44–46], this cell line could not satisfy the need for an in vivo metastatic model [47]. Unfortunately for all subsequent human osteosarcoma cell lines this fact seemed to be an important limitation. Only after characterization of the HOS cell line [48] and production of its many derivative cell lines after genetic alteration [49–53], the first in vivo tumorigenic and metastatic cell line, KRIB, later named 143B, was generated [54]. Thereafter, many cell lines were established, described in vitro and formed the basis for studying numerous cellular processes either related to cancer or not. Recently (epi)genetic, functional, and in vivo characterizations of these cell lines were published to map genetic [16] and epigenetic changes—by expression, methylation, and micro-RNA profiling—differentiation capacity and growth, invasion, and migration potential in nude mice [17]. Based on these reports, together with a previous study of drug resistance in osteosarcoma cell lines [55], appropriate cell lines can be selected for the study of interest (Figure 4).
3. In Vivo
3.1. Cell Lines in Mice
Because of the high frequency of primary tumor development and frequent pulmonary metastases when compared to human osteosarcoma cell lines [13], most often murine osteosarcoma derived cell lines have been inoculated into mice to establish in vivo models. Despite the advantage that in these syngeneic models the murine cells can grow in a murine microenvironment, these models do not contain anything of human origin. For this, human osteosarcoma cell lines have been engineered, like HOS virally transformed to 143B and chemically to MNNG, making them successfully tumorigenic and metastatic in vivo and useful in animal models [56–59], keeping in mind that a transformed cell line might not be a true representation of the human disease. Nevertheless, these mouse models proved to be excellent models for identifying factors involved in osteosarcoma migration and more importantly for screening drugs to inhibit this [19, 25, 26, 60]. The limitation of such models comes with the fact that studying fully developed osteosarcoma cells does not provide constructive information about the genesis of the tumor and its etiology. In line with this, we recently showed that candidate progenitor mesenchymal stem cells can be used to model osteosarcoma origin and first important events underlying its initiation [61–63].
This text was taken from the publication in the following link:
http://www.hindawi.com/journals/sarcoma/2012/417271/
Hoping this will be helpful,
Rafik
Dear Gabriela,
The following text fully covers the answer to your question:
2. In Vitro
2.1. Animal-Derived Cell Lines
The first successfully established metastatic osteosarcoma cell lines were derived from spontaneous mouse osteosarcoma (Figure 2) including cell lines K12 and K7M2 (developed from lung metastases of K7 cells in BALB/c mice) [13, 19, 25]. These lines were successfully proved to be metastatic and in later years used to assay the metastatic process of osteosarcoma [26]. Another murine osteosarcoma cell line, the Dunn cell line, and its derivative cell lines like LM8 were extensively used for screening new osteosarcoma drugs and studying the inhibitory effects of these compounds on angiogenesis and metastasis [27–36].
In contrast to K12 and K7M2 cells, UMR 106-01 was not a result of spontaneous osteosarcoma as it is originating from a 32P-induced tumor in a rat [37]. However, because of its in vitro and in vivo (in mouse tibia) exceptionally phenotypical similarities to human osteosarcoma, and the rapid formation of pulmonary metastasis, this cell line has been studied at length not only in osteosarcoma research [38] but also in several other bone-related studies [38–41].
A number of cell lines have been derived from spontaneous canine osteosarcoma (Figure 2). In particular, D-17 cell line originating from an osteosarcoma metastatic to the lung in an 11-year-old female poodle [42] was next to extensive use in viral studies, helpful for analyzing immunotherapy of hepatic micrometastases [43] as well as finding therapeutics for the treatment of bone cancer in dogs.
2.2. Human-Derived Cell Lines
Starting with the establishment of the first human osteosarcoma cell line named U2OS in 1964, many human osteosarcoma cell lines, such as HOS and SAOS2, have been successfully established (Figure 3). Despite comprehensive studies characterizing the U2OS cell line in vitro [44–46], this cell line could not satisfy the need for an in vivo metastatic model [47]. Unfortunately for all subsequent human osteosarcoma cell lines this fact seemed to be an important limitation. Only after characterization of the HOS cell line [48] and production of its many derivative cell lines after genetic alteration [49–53], the first in vivo tumorigenic and metastatic cell line, KRIB, later named 143B, was generated [54]. Thereafter, many cell lines were established, described in vitro and formed the basis for studying numerous cellular processes either related to cancer or not. Recently (epi)genetic, functional, and in vivo characterizations of these cell lines were published to map genetic [16] and epigenetic changes—by expression, methylation, and micro-RNA profiling—differentiation capacity and growth, invasion, and migration potential in nude mice [17]. Based on these reports, together with a previous study of drug resistance in osteosarcoma cell lines [55], appropriate cell lines can be selected for the study of interest (Figure 4).
3. In Vivo
3.1. Cell Lines in Mice
Because of the high frequency of primary tumor development and frequent pulmonary metastases when compared to human osteosarcoma cell lines [13], most often murine osteosarcoma derived cell lines have been inoculated into mice to establish in vivo models. Despite the advantage that in these syngeneic models the murine cells can grow in a murine microenvironment, these models do not contain anything of human origin. For this, human osteosarcoma cell lines have been engineered, like HOS virally transformed to 143B and chemically to MNNG, making them successfully tumorigenic and metastatic in vivo and useful in animal models [56–59], keeping in mind that a transformed cell line might not be a true representation of the human disease. Nevertheless, these mouse models proved to be excellent models for identifying factors involved in osteosarcoma migration and more importantly for screening drugs to inhibit this [19, 25, 26, 60]. The limitation of such models comes with the fact that studying fully developed osteosarcoma cells does not provide constructive information about the genesis of the tumor and its etiology. In line with this, we recently showed that candidate progenitor mesenchymal stem cells can be used to model osteosarcoma origin and first important events underlying its initiation [61–63].
This text was taken from the publication in the following link:
http://www.hindawi.com/journals/sarcoma/2012/417271/
Hoping this will be helpful,
Rafik
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