Analysis of tumor vascularization in a mouse model of metastatic lung cancer

Abstract

Therapies targeting tumor vasculature would improve the treatment of lung metastasis, although the early changes in vascular structure are incompletely understood. Here, we show that obstructive metastatic foci in lung arterioles decrease the pulmonary vascular network. To generate a mouse model of lung metastasis activation, luciferase-expressing tumor cells were inoculated into the subiliac lymph node (SiLN) of an MXH10/Mo-lpr/lpr mouse, and metastatic tumor cells in the lungs were activated by SiLN resection. Activation of metastases was monitored by in vivo bioluminescence imaging. Pulmonary blood vessel characteristics were analyzed using ex vivo micro-computed tomography. The enhanced permeability and retention (EPR) effect in neovasculature after tumor cell activation was evaluated from the accumulation of intravenously injected indocyanine green (ICG) liposomes. Metastatic foci in lung arterioles were investigated histologically. Micro-computed tomography revealed decreases in pulmonary blood vessel length, volume and number of branching nodes during the early stage of metastasis caused by metastatic foci. ICG liposome accumulation by the EPR effect was not detected. Histology identified metastatic foci in lung arterioles. The lack of an EPR effect after the formation of metastatic foci in lung arterioles makes conventional systemic chemotherapy ineffective for lung metastasis. Thus, alternative therapeutic methods of drug delivery are needed.

Artificial Light at Night Reduces Anxiety-like Behavior in Female Mice with Exacerbated Mammary Tumor Growth

“…Mouse mammary carcinoma FM3A cells were obtained from the Japanese Collection of Research Bioresources Cell Bank (Osaka, Japan). These cells are derived from a spontaneously arising mammary tumor in a C3H mouse that was initially maintained through the peritoneal cavity of C3H stock mice before being established as a cell line [41][42][43]. Typical progression of these cells has been described previously [41][42][43].…”

“…These cells are derived from a spontaneously arising mammary tumor in a C3H mouse that was initially maintained through the peritoneal cavity of C3H stock mice before being established as a cell line [41][42][43]. Typical progression of these cells has been described previously [41][42][43]. FM3A cells are metastatic and have been reported to result in lymph node and lung metastases [42,43].…”

“…Typical progression of these cells has been described previously [41][42][43]. FM3A cells are metastatic and have been reported to result in lymph node and lung metastases [42,43]. Cells were maintained as previously described [31].…”

Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination

“… 7 However, this delivery strategy using EPR effect requires the high circulation of nanoparticles in the blood and a specific physiological environment within the tumor, particularly hypervascularity. 8 Therefore, it is difficult to deliver nanoparticles to pancreatic cancer or peritoneal dissemination with hypovascularity by i.v. administration, even if the nanoparticles show excellent blood circulation.…”

Identification of Primary and Metastatic Lung Cancer-Related lncRNAs and Potential Targeted Drugs Based on ceRNA Network

“…Lung cancer is the leading cause of cancer-related mortality worldwide ( 1 ), the five-year survival rate for patients diagnosed with advanced-stage lung metastasis is only 5% ( 2 ). Therefore, lung cancer metastasis is closely related to the poor prognosis of lung cancer patients.…”