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Table 2. Non-exhaustive list of primary animal model evidence for brain-tumor interactions regulating cancer incidence,
disease progression, morbidity and mortality (see Figure 2 for more details)
Cancer type/model Main focus Primary findings Ref.
67NR/4T1/4T07 syngeneic breast Effects of peripheral tumors on central Tumors alter leptin/ghrelin signaling, [6]
cancer cells (female BalbC mice; regulation of sleep and metabolism disrupting central hypocretin/orexin
subQ/orthotopic) activity to influence glucose metabolism
and sleep via the sympathetic nervous
system
LL2 Lewis Lung carcinoma/B6 Dopaminergic regulation of tumor growth Activation of VTA-dopamine neurons [87]
(male C57bl6j mice; subQ) blunts tumor growth via sympathetic
modulation of bone-marrow myeloid
derived suppressor cells
p53 R270H©/+ WAP-Cre mutant Circadian disruption-induced cancer Chronic phase shifting accelerated [60]
model of Li-Fraumeni syndrome development spontaneous tumor growth and altered
(mouse; transgenic) tumor phenotype
N-nitroso-N-methylurea (NMU)- Effects of tumors on affective behaviors Tumor growth is associated with [141]
induced mammary tumors (rat; central cytokine concentrations, altered
chemically induced) glucocorticoid responses, and the
development of depressive-like behavior
Colon-26 adenocarcinoma cells Effects of tumors on fatigue, muscle Tumors promoted central [142,143]
(mouse; SubQ) physiology, and affective behaviors proinflammatory cytokine production and
depressive-like behavior prior to defects
in muscle function, behavior rescued by
SSRI
HeyA8, SKOV3ip1, MB-231 Effects of stress on tumor development and Stress-induced adrenergic signaling [12]
orthotopic human ovarian angiogenesis (cAMP->PKA) promotes tumor growth
carcinoma cells (nude mice; IP) and angiogenesis
Non-metastatic Effects of inflammation on central Tumors reduced hypocretin/orexin [144]
methylcholanthrene-induced hypocretin/orexin neurons and fatigue transcript expression and promoted
sarcoma (F344/NTacfBR male fatigue
rats; SubQ)
LL2 or TC-1 lung epithelial cells Role of sleep fragmentation (SF) on tumor SF accelerates tumor growth, likely [13]
(male C57Bl6 mice; subQ) growth and progression through a TLR4 dependent mechanism
LL2 Lewis Lung carcinoma cells/ Role of calcitonin-gene related peptide Inactivation of parabrachial CGRP [109]
Apc/min+ mice (male and female (CGRP) neurons in cancer-associated neurons prevents and reverses cancer-
C57Bl6; subQ/transgenic) cachexia induced anorexia, fatigue, and changes in
affective behavior
MADB106 breast cancer cells Role of dopaminergic system in tumor Smaller tumors, fewer metastases, and [84]
(outbred “hyperreactive” Wistar growth/metastasis reduced angiogenesis in rats with a
rats; subQ) hyperreactive dopaminergic system
K-ras LSL-G12D/+ ;p53 flox/flox (KP) or Effects of circadian disruption Both genetic and physiologic circadian [61]
K-ras LSL-G12D/+ (K) lung cancer (environmental and genetic) on lung tumor disruption accelerate tumor growth
model 129SvJ x C57bl6 mice (cre- growth and progression and promote c-myc upregulation and
dependent p53 deletion) metabolic reprogramming
diethylnitrosamine-induced Sympathetic nervous system effect on High density of SNS bundles associated [145]
hepatocarcinogenesis (male hepatocarcinogenesis with poor prognosis, SNS activation of
Sprague-Dawley rats) Kupffer cells drives inflammation
Hepatocarcinoma Morris Role of light and melatonin in cancer Melatonin depleted blood accelerates [79]
7288CTC cells (male buffalo rats) progression tumor growth and metabolism compared
or steroid receptor (SR)-1+ or SR- to melatonin-rich blood from healthy
1- MCF-7 human breast cancer women; light accelerates tumor growth in
xenografts (female nude rats) dose-dependent manner
B16 melanoma cells (male nude Role of peripheral dopaminergic signaling in 6-OHDA ablation of dopaminergic [146]
mice/C57bl6 D 2 receptor-KO) tumor growth/angiogenesis/metastasis nerves enhanced tumor angiogenesis
and growth, likely through D 2 -mediated
mechanism
GOS Glasgow osteosarcoma and Effect of suprachiasmatic nucleus lesions on SCN lesions drastically increased tumor [147]
pancreatic adenocarcinoma (P03) tumor growth size in both cancer models examined
xenographs (male B6D2F 1 mice;
subQ into flank)
TC-1 mouse lung cancer cells and Effect of sleep fragmentation on plasma Chronic sleep fragmentation alters the [148]
human lung adenocarcinoma exosomes and tumor growth microRNA cargo of plasma exosomes to
cells (male C57bl6 mice and promote tumor cell proliferation
obstructive sleep apnea patients)
EG, SKOV3ip1, and 222 human Effect of stress hormones on cancer Adrenergic and glucocorticoid signaling [93]
ovarian cancer cells (nude male invasiveness and growth promotes tumor invasiveness (in part)
mice) via upregulation of MMPs

VTA: ventral tegmental area; cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; 6-OHDA: 6-hydroxydopamine; MMPs:
matrix metalloproteinases