Alterations in the balance between different metabolic pathways used to meet cellular bioenergetic and biosynthetic demands are considered hallmarks of cancer. Optical imaging relying on endogenous fluorescence has been used as a noninvasive approach to assess tissue metabolic changes during cancer development. However, quantitative correlations of optical assessments with variations in the concentration of relevant metabolites or in the specific metabolic pathways that are involved have been lacking. In this study, we use high-resolution, depth-resolved imaging relying entirely on endogenous two-photon excited fluorescence in combination with invasive biochemical assays and mass spectrometry to demonstrate the sensitivity and quantitative nature of optical redox ratio tissue assessments. We identify significant differences in the optical redox ratio of live, engineered normal and precancerous squamous epithelial tissues. We establish that while decreases in the optical redox ratio are associated with enhanced levels of glycolysis relative to oxidative phosphorylation, increases in glutamine consumption to support energy production are associated with increased optical redox ratio values. Such mechanistic insights in the origins of optical metabolic assessments are critical for exploiting fully the potential of such noninvasive approaches to monitor and understand important metabolic changes that occur in live tissues at the onset of cancer or in response to treatment. Cancer Res; 1–9. ©2014 AACR.
Myeloid Cell Wnt7b Mediates Angiogenic Switch and Metastasis
Oncogenic targets acting in both tumor cells and tumor stromal cells may offer special therapeutic appeal. Interrogation of the Oncomine database revealed that 52 of 53 human breast carcinomas showed substantial upregulation of WNT family ligand WNT7B. Immunolabeling of human mammary carcinoma showed that WNT7B immunoreactivity was associated with both tumor cells and with tumor-associated macrophages. In the MMTV-PymT mouse model of mammary carcinoma, we found tumor progression relied upon WNT7B produced by myeloid cells in the microenvironment. Wnt7b deletion in myeloid cells reduced the mass and volume of tumors due to a failure in the angiogenic switch. In the tumor overall, there was no change in expression of Wnt/β-catenin pathway target genes, but in vascular endothelial cells (VEC), expression of these genes was reduced, suggesting that VECs respond to Wnt/β-catenin signaling. Mechanistic investigations revealed that failure of the angiogenic switch could be attributed to reduced Vegfa mRNA and protein expression in VECs, a source of VEGFA mRNA in the tumor which was limiting in the absence of myeloid WNT7B. We also noted a dramatic reduction in lung metastasis associated with decreased macrophage-mediated tumor cell invasion. Together, these results illustrated the critical role of myeloid WNT7B in tumor progression, acting at the levels of angiogenesis, invasion, and metastasis. We suggest that therapeutic suppression of WNT7B signaling might be advantageous due to targeting multiple aspects of tumor progression. Cancer Res; 1–12. ©2014 AACR.
Aspirin Benefits Some at Risk for Colon Cancer
Join us for a FREE Skin Cancer Prevention Conference
Penn’s Abramson Cancer Center invites you and your loved ones to attend CANPrevent Skin Cancer, a free educational conference for anyone interested in learning about preventing skin cancer.
CANPrevent Skin Cancer is designed to address the personal and medical issues facing those at risk for skin cancer. The conference provides patient-focused information about the latest advances in skin cancer risk, screening and prevention.
Who Should Attend
Anyone interested in learning about skin cancer and its prevention – especially those with:
- Natural blond or red hair color
- Presence of atypical or numerous moles
- Sun sensitivity (easily burns, difficulty tanning)
- History of excessive sun exposure, including sunburns
- History of using tanning booths
- History of diseases that suppress the immune system
- Personal or family history of melanoma, basal cell or squamous cell skin cancers
Join Us
Time: 8 to 11 am
Date: Friday, May 16, 2014
Location: Hilton Hotel located at 4200 City Avenue, Philadelphia, PA
Registration: Register here call 800-789-PENN (7366)
Cost: FREE
Get the facts on skin cancer and melanoma risk, prevention and screening – they could save your life or the life of someone you know.
Unable to Attend?
Follow Penn Medicine on Twitter for event information before the conference date, and live tweeting throughout the conference with the hashtag #SkinCancerACC.
Please “re-tweet” and share Penn Medicine’s messages about skin cancer prevention and awareness with your followers.
FREE Skin Cancer Screening
Have your skin checked by a Penn dermatologist to determine your risk for developing skin cancer.
Date: Saturday, May 17, 2014
Location: Smilow Center for Research, attached to the Perelman Center for Advanced Medicine (PCAM)
Appointments are necessary and space is limited.
Call 215- 662- 2737 to make your reservation.
Join Us For a FREE Melanoma Conference
Penn’s Abramson Cancer Center invites patients, family members and anyone interested in learning about melanoma risk, prevention, diagnosis and treatment to attend Focus On Melanoma.
Focus On Melanoma is a free educational conference featuring a keynote address by Singer/Songwriter and Survivor, Charlie Lustman,
Penn’s Focus On Melanoma Conference addresses the personal and medical issues facing people with melanoma including those in treatment, survivors, their loved ones, relatives and caregivers.
The conference provides patient-focused information on the latest advances in melanoma risk, prevention, diagnosis, treatment, symptom management and psychosocial issues. It is also an opportunity to network and gain support from other melanoma patients and survivors.
Who Should Attend
- People newly diagnosed with melanoma
- Those at risk for melanoma
- Melanoma survivors
- Family members, caregivers or health care providers of melanoma patients/survivors
- Those diagnosed with a pigmented lesion and their family members/caregivers
Join Us
Time: 8 am to 3 pm
Date: Friday May 16, 2014
Location: Hilton Hotel located at 4200 City Avenue, Philadelphia, PA
Registration: Register here or call 800-789-PENN (7366)
Cost: FREE
Unable to Attend?
If you are unable to attend in person, follow Penn Medicine on Twitter for event information before the conference date, and live tweeting throughout the conference with the hashtag #MelanomaACC.
FREE Skin Cancer Screening
Have your skin checked by a Penn dermatologist to determine your risk for developing skin cancer.
Date: Saturday, May 17, 2014
Location: Smilow Center for Research (attached to the Perelman Center for Advanced Medicine- PCAM)
Appointments are necessary and space is limited.
Call 215- 662- 2737 to make your reservation.
