Amit Lab in Action
Our research focus is split evenly between experimental cancer cell biology and studying tumor microenvironment subpopulations using computational biology approaches. We develop new experimental methods to isolate and sequence neural niche subpopulations and apply analytical approaches to study how solid tumors sculpt their microenvironment. We focus mainly on head and neck cancer to understand the role of the peripheral nervous system in the evolution of invasion, metastasis, and response to chemotherapy. Our goal is to understand the role of neural signaling in tumor evolution so that we can exploit these signals for therapeutic vulnerabilities and enhance cancer therapy. We fully expect that applying these tools to patients will ultimately inform key areas of cancer research including the prevention and treatment of cancer.
Research
Amit Lab in Action
Our research focus is split evenly between experimental cancer cell biology and studying tumor microenvironment subpopulations using computational biology approaches. We develop new experimental methods to isolate and sequence neural niche subpopulations and apply analytical approaches to study how solid tumors sculpt their microenvironment. We focus mainly on head and neck cancer to understand the role of the peripheral nervous system in the evolution of invasion, metastasis and response to chemotherapy. Our goal is to understand the role of neural signaling in tumor evolution so that we can exploit these signals for therapeutic vulnerabilities and enhance cancer therapy. We fully expect that applying these tools to patients will ultimately inform key areas of cancer research including the prevention and treatment of cancer.
Experimental Models used for Neural-Cancer Cell Interaction
[insert image: experimental_models]
One main reason that understanding mechanisms of neural tracking is challenging is the lack of reliable and reproducible experimental models for neural invasion. The in vitro dorsal root ganglia (DRG) assay (figure), designed for studying the neurotropic ability of cancer cells, also enables modulation of paracrine signaling by controlling chemoattractants and by signaling between cancer cells and the DRG. Neurite outgrowth, directionality and Euclidean velocity of cancer cells can be measured before cancer–neuron contact has been established. However, the importance of various cellular components in the classical perineural niche, including Schwann cells and fibroblasts, cannot be directly addressed in this model.
In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model
Solid tumors disseminate in three main ways: direct invasion, lymphatic spread, and hematogenic spread. However, there is a fourth means of cancer spread that is frequently disregarded: dissemination along nerves. This video article shows the use of the dorsal root ganglia (DRG)/cancer cell model in pancreatic ductal adenocarcinoma.
[link to https://www.jove.com/video/52990/in-vitro-modeling-cancerous-neural-invasion-dorsal-root-ganglion]
Cancer cell invasion along the neurons of the dorsal root ganglia (DRG)
[insert image: invasion_DRG}
a. DRG (up) and cancer cells (bottom) on day 0 after seeding. b. DRG and cancer cells on day 7 after seeding. c. DRG extracted from GFP model and cancer cells. d. cancer cells migrate along the DRG neuron (arrows).
Evolution of Malignant Precursor Lesion that Promotes Cancer Cell Invasion into the Nerve
As a malignant precursor lesion evolves, the perineural niche starts to assemble to form a cellular and biochemical microenvironment that can eventually promote cancer cell invasion into the nerve (panel a). At a certain point, these neurogenic cues initiate axonogenesis, which is accompanied by recruitment of stromal cells typical of the perineural niche (panel b). Subsequent malignant transformation results in the release of multiple chemotactic cues, which promotes further recruitment of inflammatory cells to establish the perineural niche (panel c). Within the niche, an injured nerve serves as a portal for invasion while neural homeostasis including Wallerian degeneration and nerve regeneration is maintained (panel d). At the perineural niche, the injured nerve maintains regeneration via nerve growth factor secretion that further nourishes the inflammatory response and leads to immune cell recruitment.
Research
Amit Lab in Action
Our research focus is split evenly between experimental cancer cell biology and studying tumor microenvironment subpopulations using computational biology approaches. We develop new experimental methods to isolate and sequence neural niche subpopulations and apply analytical approaches to study how solid tumors sculpt their microenvironment. We focus mainly on head and neck cancer to understand the role of the peripheral nervous system in the evolution of invasion, metastasis and response to chemotherapy. Our goal is to understand the role of neural signaling in tumor evolution so that we can exploit these signals for therapeutic vulnerabilities and enhance cancer therapy. We fully expect that applying these tools to patients will ultimately inform key areas of cancer research including the prevention and treatment of cancer.
Experimental Models used for Neural-Cancer Cell Interaction
[insert image: experimental_models]
One main reason that understanding mechanisms of neural tracking is challenging is the lack of reliable and reproducible experimental models for neural invasion. The in vitro dorsal root ganglia (DRG) assay (figure), designed for studying the neurotropic ability of cancer cells, also enables modulation of paracrine signaling by controlling chemoattractants and by signaling between cancer cells and the DRG. Neurite outgrowth, directionality and Euclidean velocity of cancer cells can be measured before cancer–neuron contact has been established. However, the importance of various cellular components in the classical perineural niche, including Schwann cells and fibroblasts, cannot be directly addressed in this model.
In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model
Solid tumors disseminate in three main ways: direct invasion, lymphatic spread, and hematogenic spread. However, there is a fourth means of cancer spread that is frequently disregarded: dissemination along nerves. This video article shows the use of the dorsal root ganglia (DRG)/cancer cell model in pancreatic ductal adenocarcinoma.
[link to https://www.jove.com/video/52990/in-vitro-modeling-cancerous-neural-invasion-dorsal-root-ganglion]
Cancer cell invasion along the neurons of the dorsal root ganglia (DRG)
[insert image: invasion_DRG}
a. DRG (up) and cancer cells (bottom) on day 0 after seeding. b. DRG and cancer cells on day 7 after seeding. c. DRG extracted from GFP model and cancer cells. d. cancer cells migrate along the DRG neuron (arrows).
Evolution of Malignant Precursor Lesion that Promotes Cancer Cell Invasion into the Nerve
As a malignant precursor lesion evolves, the perineural niche starts to assemble to form a cellular and biochemical microenvironment that can eventually promote cancer cell invasion into the nerve (panel a). At a certain point, these neurogenic cues initiate axonogenesis, which is accompanied by recruitment of stromal cells typical of the perineural niche (panel b). Subsequent malignant transformation results in the release of multiple chemotactic cues, which promotes further recruitment of inflammatory cells to establish the perineural niche (panel c). Within the niche, an injured nerve serves as a portal for invasion while neural homeostasis including Wallerian degeneration and nerve regeneration is maintained (panel d). At the perineural niche, the injured nerve maintains regeneration via nerve growth factor secretion that further nourishes the inflammatory response and leads to immune cell recruitment.
Experimental Models used for Neural-Cancer Cell Interaction
One main reason that understanding mechanisms of neural tracking is
challenging is the lack of reliable and reproducible experimental
models for neural invasion. The in vitro dorsal root ganglia (DRG)
assay (figure), designed for studying the neurotropic ability of
cancer cells, also enables modulation of paracrine signaling by
controlling chemoattractants and by signaling between cancer cells and
the DRG. Neurite outgrowth, directionality, and Euclidean velocity of
cancer cells can be measured before cancer–neuron contact has been
established. However, the importance of various cellular components in
the classical perineural niche, including Schwann cells and
fibroblasts, cannot be directly addressed in this model.
Cancer cell invasion along the neurons of the dorsal root ganglia (DRG)
In Vitro Modeling of Cancerous Neural Invasion: The Dorsal
Root Ganglion Model
Solid tumors disseminate in three main ways: direct invasion, lymphatic spread, and hematogenic spread. However, there is a fourth means of cancer spread that is frequently disregarded: dissemination along nerves. This video article shows the use of the dorsal root ganglia (DRG)/cancer cell model in pancreatic ductal adenocarcinoma.
Evolution of Malignant Precursor Lesion that Promotes Cancer Cell Invasion into the Nerve
As a malignant precursor lesion evolves, the perineural niche starts
to assemble to form a cellular and biochemical microenvironment that
can eventually promote cancer cell invasion into the nerve (panel a).
At a certain point, these neurogenic cues initiate axonogenesis, which
is accompanied by the recruitment of stromal cells typical of the
perineural niche (panel b). Subsequent malignant transformation
results in the release of multiple chemotactic cues, which promotes
further recruitment of inflammatory cells to establish the perineural
niche (panel c). Within the niche, an injured nerve serves as a portal
for invasion while neural homeostasis including Wallerian degeneration
and nerve regeneration is maintained (panel d). At the perineural
niche, the injured nerve maintains regeneration via nerve growth
factor secretion that further nourishes the inflammatory response and
leads to immune cell recruitment.