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Figure 3: Karyogram of HT1376 with GTL banding. The chromosomes with changes are marked within square with letters that represent
partial metaphases with GTL and FISH subtelomeric probes. GTL: giemsa trypsin leishman banding; FISH: fluorescent in situ hibridization

that the use of both PI3K and mTOR inhibitors would respectively. [10,44] To achieve reliable tumor take after
be beneficial in these cases. [39] We further evaluated the transurethral implantation of tumor cells, the host bladder
combined effect of mTOR inhibitors with gemcitabine is usually submitted to catheterization with chemical
and cisplatin, which are currently used in the treatment pre-treatment or mechanical traumatization. Although
of MIBC. The combined therapy resulted in enhanced widely used, these methods are often associated with
inhibition of cell proliferation, increased apoptosis and adverse reactions in some study animals and can lead to
autophagy, especially in 5637 and HT1376 cell lines, uncontrolled tumor growth in adjacent organs. On the
when compared with gemcitabine or cisplatin alone. In other hand, the injection of tumor cells into the bladder
contrast, in the T24 cell line, the addition of everolimus wall frequently relies on laparotomy and mobilization
or temsirolimus to cisplatin did not increase the efficacy of the bladder, also a morbidity-associated procedure.
of the latter one but, when combined to gemcitabine More recently, ultrasound guided percutaneous
resulted in enhanced cell proliferation inhibition. [40-43] implantation of cells between the urothelium and lamina
This evidence supports the role of complex tumor propria have been reported with the benefit of accurate
signaling pathways in tumor behavior and response to cell delivery and a minimally invasive procedure. [45]
chemotherapy and highlights the diverse and sometimes Bladder palpation and urine inspection are the initial
controversial results observed in preclinical studies. approaches to identify growing tumors, followed by
imaging techniques such as ultrasound, magnetic
To some extent, the cell lines used in our investigation resonance imaging and bioluminescence. [45,46] Inclusion
reflect the tumor heterogeneity and its response to of fluorescent or luciferase reporter genes in tumor cells
anticancer drugs. Knowing the limitations of this study prior to implantation enables in vivo imaging of tumors
material, the use of cell lines can be a very important and metastases, and this method has been validated in
starting point, indicating new research opportunities. mouse orthotopic models with promising results. [47]
However, evidence from in vitro studies must be further
confirmed using more realistic and complex models such CONCLUSION
as xenografts.
UBC is a complex disease with both genetic and
In addition to in vitro assays, human cell lines have environmental factors playing a role in tumor initiation,
been widely used to establish xenograft models in mice. progression, and metastasis. In addition to the models
In this model, tumor cells are implanted either under used by our group, many more have been developed and
the skin (heterotopic) or in the bladder (orthotopic). In are available to study the molecular biology, behavior,
orthotopic models, the tumor arises within the bladder and chemosensitivity of UBC.
of the recipient host allowing the study of tumor cells
behavior in the normal host tissue microenvironment. Most murine orthotopic UBC models can be obtained by
Single cell suspensions of bladder cancer cell lines three ways such as induced by a chemical carcinogen,
can be inoculated by intravesical instillation or direct implantation of human UBC cells in immunocompromised
injection into the bladder wall to establish xenografts or mice, or implantation of murine UBC cells in
syngeneic models, if using human cell lines or mouse/ immunocompetent mice (allograft or syngeneic models).
rat cell lines in the corresponding background strain, The model characteristics will depend on the site of

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ Issue 2 ¦ February 29, 2016 ¦ 55